JP5924658B2 - Concentration determination apparatus, light absorption coefficient calculation method, equivalent scattering coefficient calculation method, concentration determination method, program for calculating light absorption coefficient, and program for calculating concentration - Google Patents

Description

  Some aspects of the present invention include a concentration quantification apparatus, a light absorption coefficient calculation method, and an equivalent scattering coefficient calculation for quantifying the concentration of a target component in an arbitrary layer among observation targets formed from a plurality of light scattering medium layers. The present invention relates to a method, a concentration determination method, a program for calculating a light absorption coefficient, and a program for calculating a concentration.

  Conventionally, the blood sugar level has been measured by collecting blood from a fingertip or the like and measuring the enzyme activity for glucose in the blood. However, such a blood glucose level measurement method requires blood sampling from a fingertip or the like, and is troublesome and painful in blood sampling, or requires a measurement chip to attach blood. There is a demand for a non-invasive blood glucose level measurement method that does not require a blood pressure.

  Then, the method of irradiating near infrared light to skin and calculating | requiring the density | concentration of glucose from the light absorption amount is examined (for example, refer patent document 1). Specifically, a calibration curve indicating the relationship between the glucose concentration, the wavelength of light to be irradiated, and the amount of light absorbed is prepared in advance, a certain wavelength range is scanned using a monochromator, etc. The amount of absorption with respect to the wavelength is obtained, and the glucose concentration is calculated by comparing the wavelength and the amount of absorption with a calibration curve.

Japanese Patent No. 3931638

  However, since the conventional non-invasive blood sugar level measurement method measures the near-infrared spectrum of the dermis layer by determining the distance between the light input and output, the measured spectrum includes not only the spectrum of the dermis layer but also the epidermis layer. The spectrum of the subcutaneous tissue layer was also included, and there was a problem that the observed change in the light absorption coefficient included noise due to the epidermis layer or the subcutaneous tissue layer.

  The present invention has been made in view of the above points, and its purpose is to reduce the influence of noise caused by layers other than the target layer, a concentration determination device, a light absorption coefficient calculation method, an equivalent scattering coefficient calculation method, a concentration determination. A method, a program for calculating a light absorption coefficient, and a program for calculating a concentration are provided.

One aspect of the present invention is a light absorption coefficient calculation method for calculating a light absorption coefficient in an arbitrary layer among observation targets formed from a plurality of light scattering medium layers, in which the irradiation unit is a short-time pulse. Intensity of light backscattered by the observation object at a predetermined time after light irradiation, equivalent scattering coefficient of propagation path of light received by the first light receiving means or the second light receiving means, arbitrary A model of propagation optical path length distribution in each of the layers of the plurality of light scattering media generated based on the equivalent scattering coefficient at the time of the time, the short time generated based on the equivalent scattering coefficient at an arbitrary time A model of a time-resolved waveform of pulsed light, an optical path length of each of the layers of the light scattering medium at the predetermined time of the model of the propagation optical path length distribution, the short-time pulsed light A first step of acquiring the light intensity at the predetermined time of the model of the time-resolved waveform, the light intensity acquired in the first step, and the optical path length of each of the layers of the plurality of light scattering media And a second step of calculating a light absorption coefficient of the arbitrary layer based on the light intensity model.
According to one aspect of the present invention, the observation target has a laminated structure of n layers or more, and the equivalent scattering coefficient of the propagation path of the light received by the first light receiving means or the second light receiving means is μ _s ′ (t), The equivalent scattering coefficient of the m layer is μ _sm ′, the average optical path length of the mth layer at time t is L _m ′ (t), the optical path length of the mth layer at time t is L _m (t), and the short-time pulse light When the light intensity at time t of the model of the time-resolved waveform is N (t), the light intensity at least for a predetermined time τ1 to τ2 is acquired, and a plurality of light scattering media are obtained from the following equation (2). An approximate solution of the equivalent scattering coefficient of each layer is calculated, and each of the layers of the plurality of light scattering media at the time t of the propagation path length distribution model generated from the approximate solution of the equivalent scattering coefficient is calculated. Before the correction of the optical path length of the layer and the model of the time-resolved waveform of the short-time pulse light The correction value of the light intensity at a predetermined time is obtained, and the correction value of the optical path length and the correction value of the light intensity model are substituted into the following equation (2), and the plurality of light scattering media By repeatedly calculating the correction value of the equivalent scattering coefficient of each layer of the layers until it converges to the true value of the equivalent scattering coefficient of each of the layers of the plurality of light scattering media, An equivalent scattering coefficient calculation method characterized by calculating an equivalent scattering coefficient.
One aspect of the present invention includes a computer, an irradiation unit that irradiates an observation target formed of a plurality of light scattering medium layers with a short-time pulsed light, and the short-time pulsed light is backscattered by the observation target. A first light receiving means for receiving light, and light received by the short-time pulsed light backscattered by the observation target, and rearward by the observation target from an irradiation position where the observation target is irradiated with the short-time pulsed light. A second light receiving means disposed so that a distance to a position for receiving scattered light is different from that of the first light receiving means; and the first light receiving means at a predetermined time after a time when the irradiation means emits short-time pulse light. First light intensity acquisition means for acquiring the intensity of light received by the light receiving means; and the second light receiving means at a predetermined time after the time when the irradiation means irradiates the pulse light for a short time. Based on the second light intensity acquisition means for acquiring the intensity of the received light, the light intensity acquired by the first light intensity acquisition means, and the light intensity acquired by the second light intensity acquisition means, the first light reception Or the first equivalent scattering coefficient calculating means for calculating the equivalent scattering coefficient of the propagation path of the light received by the second light receiving means, and the equivalent scattering coefficient at an arbitrary time calculated by the first equivalent scattering coefficient calculating means. The optical path length distribution storage means for storing the propagation path length distribution model in each of the layers of the plurality of light scattering media generated by the above, and the equivalent at any time calculated by the first equivalent scattering coefficient calculation means The time-resolved waveform storage means for storing the time-resolved waveform model of the short-time pulsed light generated based on the scattering coefficient, and the optical path length distribution storage means from the propagation path length distribution model The optical path length acquisition means for acquiring the optical path length of each of the layers of the plurality of light scattering media at a fixed time, and the time-resolved waveform storage means, the time-resolved waveform model of the time-resolved waveform model Light intensity model acquisition means for acquiring light intensity at a predetermined time and the first light intensity acquisition means or the second light intensity acquisition means, or the first light intensity acquisition and the second light intensity acquisition means Light intensity acquired by different third light intensity acquisition means, optical path length of each of the layers of the plurality of light scattering media acquired by the optical path length acquisition means, and light intensity acquired by the light intensity model acquisition means A program for calculating a light absorption coefficient for functioning as a light absorption coefficient calculation means for calculating a light absorption coefficient of an arbitrary layer based on the model.
Some aspects of the present invention have been made in order to solve the above-described problem, and a concentration for quantifying the concentration of a target component in an arbitrary layer among observation targets formed from a plurality of light scattering medium layers. An quantification device, wherein an irradiating means for irradiating the observation target with a short-time pulsed light, a first light-receiving means for receiving the light back-scattered by the observation target by the short-time pulsed light, and the short-time pulsed light The first light receiving means receives the light backscattered by the observation target and the distance from the irradiation position at which the short time pulse light is irradiated to the observation target to the position at which the light backscattered by the observation target is received. The second light receiving means arranged differently from the first light receiving means, and the intensity of the light received by the first light receiving means at a predetermined time after the time when the irradiating means irradiated the short-time pulse light. First light intensity acquisition means, second light intensity acquisition means for acquiring the intensity of light received by the second light receiving means at a predetermined time after the time when the irradiation means irradiates the pulse light for a short time, Based on the light intensity acquired by the one light intensity acquisition means and the light intensity acquired by the second light intensity acquisition means, the equivalent scattering coefficient of the propagation optical path of the light received by the first light receiving means or the second light receiving means A first equivalent scattering coefficient calculating means for calculating the first scattering coefficient, and an equivalent scattering coefficient at an arbitrary time calculated by the first equivalent scattering coefficient calculating means for each of the layers of the plurality of light scattering media. Time resolution of the short-time pulse light generated based on an equivalent scattering coefficient at an arbitrary time calculated by the first equivalent scattering coefficient calculating means and an optical path length distribution storing means for storing a propagation optical path length distribution model An optical path length of each of the layers of the plurality of light scattering media at the predetermined time of the model of the propagation optical path length distribution from the time-resolved waveform storage means for storing the shape model and the optical path length distribution storage means An optical path length acquisition means for acquiring the light intensity model acquisition means for acquiring the light intensity at the predetermined time of the time-resolved waveform model of the short-time pulsed light from the time-resolved waveform storage means, and the first Light intensity acquired by a third light intensity acquisition means different from the light intensity acquisition means or the second light intensity acquisition means, or the first light intensity acquisition means and the second light intensity acquisition means, and the optical path length acquisition means The light for calculating the light absorption coefficient of the arbitrary layer based on the optical path length of each of the layers of the plurality of light scattering media acquired by and the light intensity model acquired by the light intensity model acquisition means Absorption coefficient And a concentration calculating means for calculating the concentration of the target component in the arbitrary layer based on the light absorption coefficient calculated by the light absorption coefficient calculating means.

  According to this configuration, the light intensity acquired by the first light intensity acquisition unit, the second light intensity acquisition unit, or the third light intensity acquisition unit, and each of the layers of the plurality of light scattering media acquired by the optical path length acquisition unit Based on the optical path length of the layer and the light intensity model acquired by the light intensity model acquisition means, the light absorption coefficient of an arbitrary layer can be selectively calculated. Also, the model of the propagation optical path length distribution and the model of the time-resolved waveform to be observed are equivalently scattered at an arbitrary time based on the intensity of the backscattered light received by the two light receiving means of the first light receiving means and the second light receiving means. A method of generating by coefficients is adopted. Thereby, it is possible to suppress the occurrence of an error factor when calculating the light absorption coefficient of an arbitrary layer, and to calculate the light absorption coefficient of an arbitrary layer with high accuracy.

Further, according to some aspects of the present invention, the equivalent scattering coefficient of the propagation path of light received by the first light receiving unit or the second light receiving unit is μ _s ′ (t), and the speed of light in the scatterer is set. c, a distance from an irradiation position at which the observation target is irradiated with the short-time pulsed light to a position at which the first light receiving unit receives light backscattered by the observation target, ρ ₁ , and a distance from the irradiation position to the second The distance to the position where the light receiving means receives the light backscattered by the observation target is ρ ₂ , the light intensity acquired by the first light intensity acquisition means at time t is R (ρ ₁ , t), and the second light. When the light intensity acquired by the intensity acquisition unit at time t is R (ρ ₂ , t), the first equivalent scattering coefficient calculation unit calculates the first light receiving unit or the second unit from the following equation (1). Equivalent scattering of the propagation path of light received by the light receiving means It calculates the number, characterized in that.

  According to this configuration, the equivalent scattering coefficient at an arbitrary time is calculated by the above equation (1). Therefore, the equivalent scattering coefficient time function of the light propagation optical path can be calculated with high accuracy.

  Further, according to some aspects of the present invention, an optical path length of each of the layers of the plurality of light scattering media acquired by the optical path length acquisition unit, a light intensity model acquired by the light intensity model acquisition unit, 2nd equivalent scattering coefficient calculation means for calculating an equivalent scattering coefficient of the arbitrary layer based on the first light intensity acquisition means or the second light intensity acquisition means, or The light intensity acquired by the third light intensity acquisition unit, the optical path length of each of the layers of the plurality of light scattering media acquired by the optical path length acquisition unit, and the light intensity acquired by the light intensity model acquisition unit The light absorption coefficient of the arbitrary layer is calculated based on the model and the equivalent scattering coefficient of the arbitrary layer calculated by the second equivalent scattering coefficient calculating means.

  According to this configuration, the light intensity acquired by the first light intensity acquisition unit, the second light intensity acquisition unit, or the third light intensity acquisition unit, and each of the layers of the plurality of light scattering media acquired by the optical path length acquisition unit The light absorption coefficient of an arbitrary layer based on the optical path length of the layer, the light intensity model acquired by the light intensity model acquisition means, and the equivalent scattering coefficient of the arbitrary layer calculated by the second equivalent scattering coefficient calculation means Can be calculated selectively. Since the equivalent scattering coefficient is taken into account when calculating the light absorption coefficient, the calculation result of the light absorption coefficient is highly accurate. Therefore, by calculating the concentration of the target component based on the calculated light absorption coefficient, it is possible to reduce the influence of noise due to other layers and perform highly accurate concentration quantification.

In some embodiments of the present invention, the observation target has a laminated structure of n layers or more, and an equivalent scattering coefficient of a light propagation path of light received by the first light receiving unit or the second light receiving unit is expressed as μ _s ′. (T), the equivalent scattering coefficient of the m-th layer is μ _sm , the average optical path length of the m-th layer at time t is L _m ′ (t), the optical path length of the m-th layer at time t is L _m (t), When the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light is N (t), the light intensity acquisition means acquires the light intensity at least for a predetermined time τ1 to τ2, The second equivalent scattering coefficient calculating means calculates an approximate solution of an equivalent scattering coefficient of each of the plurality of light scattering medium layers from the following equation (2), and is generated from the approximate solution of the equivalent scattering coefficient. The plurality of light scattering media at the predetermined time of the propagation optical path length distribution model A correction value of the optical path length of each layer of the quality layer and a correction value of the light intensity at the predetermined time of the time-resolved waveform model of the short-time pulsed light, and the correction value of the optical path length And calculating the correction value of the equivalent scattering coefficient of each of the layers of the plurality of light scattering media by substituting the correction value of the light intensity model and the correction value of the light intensity model into the following equation (2): It is characterized in that the equivalent scattering coefficient of the arbitrary layer is calculated by repeatedly performing until it converges to the true value of the equivalent scattering coefficient of each layer of the medium.

  According to this configuration, when calculating the equivalent scattering coefficient, iterative calculation using the above equation (2) is performed until it converges to the true value of the equivalent scattering coefficient. Therefore, the equivalent scattering coefficient of an arbitrary layer can be calculated with high accuracy.

Further, according to some aspects of the present invention, the observation target has a laminated structure of n layers or more, the light intensity at time t of the model of the time-resolved waveform of the short-time pulsed light is N (t), and the light intensity The light intensity acquired by the acquisition means at time t is R (t), the light absorption coefficient of the m-th layer is μ _am , and the optical path length of the m-th layer at time t in the model of the propagation optical path length distribution is L _m (t) When the number of incident photons is N _in and the incident light intensity is I _in , the light intensity acquisition means acquires light intensity at a plurality of times t _{1 to} t _m , and the light absorption coefficient calculation means The light absorption coefficient of the arbitrary layer is calculated from the equation (3).

  According to this configuration, the light absorption coefficient of an arbitrary layer is calculated by the above equation (3). Therefore, the light absorption coefficient of an arbitrary layer can be calculated with high accuracy.

Further, according to some aspects of the present invention, the observation target has a laminated structure of n layers or more, the light intensity at time t of the model of the time-resolved waveform of the short-time pulsed light is N (t), and the light intensity The light intensity acquired by the acquisition means at time t is R (t), the light absorption coefficient of the m-th layer is μ _am , and the optical path length of the m-th layer at time t in the model of the propagation optical path length distribution is L _m (t) When the number of incident photons is N _in and the incident light intensity is I _in , the light intensity acquisition means acquires the light intensity between a predetermined time and at least a predetermined time τ1 to τ2, and the light absorption coefficient The calculating means calculates the light absorption coefficient of the arbitrary layer from the following equation (4).

  According to this configuration, since the light absorption coefficient is calculated by the integral value of the optical path length between the times τ1 and τ2, the influence on the calculation result of the light absorption coefficient due to the error included in the measured light reception intensity can be reduced. it can.

Further, according to some aspects of the present invention, the observation target has a laminated structure of n layers or more, the light absorption coefficient in the m-th layer that is the arbitrary layer is μ _am , and the i-th component that forms the observation target _Where the light absorption coefficient is μ _ai and the volume concentration of the i-th component forming the observation target is c _vi , the concentration calculation means calculates the target component in the arbitrary layer from the following equation (5): The density is calculated.

  According to this structure, the density | concentration of the target component in arbitrary layers is computed by said (5) Formula. Therefore, the concentration of the target component in any layer can be calculated with high accuracy.

Further, according to some aspects of the present invention, the observation target has a laminated structure of n layers or more, the light absorption coefficient in the m-th layer that is the arbitrary layer is μ _am , and the i-th component that forms the observation target the molar extinction coefficient epsilon _i, the molar concentration of the i component forming the observation target is taken as c _i, the concentration calculating means, the following (6) from the equation of the target component in the arbitrary layer The density is calculated.

  According to this configuration, the concentration of the target component in an arbitrary layer is calculated by the above equation (6). Therefore, the concentration of the target component in any layer can be calculated with high accuracy.

  Further, according to some aspects of the present invention, the concentration calculation unit generates a calibration curve from values obtained by measuring a characteristic whose characteristics are known using multivariate analysis based on the light absorption coefficient in the arbitrary layer. Then, the concentration of the target component in the arbitrary layer is calculated by collating the measurement value of the unknown measurement target with a calibration curve.

  In some embodiments of the present invention, when the observation target is skin and the arbitrary layer is a dermis layer, the concentration of glucose contained in the dermis layer is quantified.

  According to this configuration, by calculating the concentration of glucose contained in the dermis layer based on the calculated light absorption coefficient, it is possible to reduce the influence of noise caused by other layers and to determine the glucose concentration with high accuracy. Can do.

  Further, some aspects of the present invention are light absorption coefficient calculation methods for calculating a light absorption coefficient in an arbitrary layer among observation targets formed from a plurality of light scattering medium layers, wherein the irradiation means is short. The intensity of the light back-scattered by the observation target at the predetermined time after the time pulse light irradiation, the equivalent of the propagation path of the light received by the first light receiving means or the second light receiving means A scattering coefficient, a model of propagation path length distribution in each layer of the plurality of light scattering medium layers generated based on the equivalent scattering coefficient at an arbitrary time, and generated based on the equivalent scattering coefficient at an arbitrary time In addition, the time-resolved waveform model of the short-time pulsed light, the propagation optical path length distribution model, the optical path length of each of the layers of the plurality of light scattering media at the predetermined time, the short time A first step of acquiring the light intensity at the predetermined time of the time-resolved waveform model of the pulsed light; the light intensity acquired in the first step; and each of the layers of the plurality of light scattering media And a second step of calculating a light absorption coefficient of the arbitrary layer based on the optical path length and the light intensity model.

  According to this method, the light absorption coefficient of an arbitrary layer is selectively selected based on the light intensity acquired in the first step, the optical path length of each layer of the plurality of light scattering media, and the light intensity model. Can be calculated. In addition, a method of generating a propagation optical path length distribution model and a time-resolved waveform model to be observed based on an equivalent scattering coefficient at an arbitrary time is adopted. Thereby, it is possible to suppress the occurrence of an error factor when calculating the light absorption coefficient of an arbitrary layer, and to calculate the light absorption coefficient of an arbitrary layer with high accuracy.

In some embodiments of the present invention, the equivalent scattering coefficient of the propagation optical path of light received by the first light receiving means or the second light receiving means is μ _s ′ (t), the speed of light in the scatterer is c, The distance from the irradiation position at which the observation target is irradiated with the short-time pulse light to the position at which the first light receiving unit receives the light backscattered by the observation target is represented by ρ ₁ , and the second light receiving unit from the irradiation position. Is the distance to the position for receiving the light backscattered by the observation object, ρ ₂ , the light intensity acquired by the first light intensity acquisition means at time t is R (ρ ₁ , t), and the second light intensity acquisition When the light intensity acquired by the means at time t is R (ρ ₂ , t), in the first step, the first light receiving means or the second light receiving means receives light from the following equation (1). Calculate the equivalent scattering coefficient of the light propagation path, And wherein the door.

  According to this method, the equivalent scattering coefficient at an arbitrary time is calculated by the above equation (1). Therefore, the equivalent scattering coefficient time function of the light propagation optical path can be calculated with high accuracy.

  Further, according to some aspects of the present invention, in the first step, the equivalent scattering of the arbitrary layer based on the optical path length of each of the layers of the plurality of light scattering media and the light intensity model. A coefficient is obtained, and in the second step, the light intensity obtained in the first step, the optical path length of each of the layers of the plurality of light scattering media, the light intensity model, and the arbitrary layer The light absorption coefficient of the arbitrary layer is calculated based on the equivalent scattering coefficient.

  According to this method, in the second step, the light intensity acquired in the first step, the optical path length of each of the layers of the plurality of light scattering media, the light intensity model, the equivalent scattering coefficient of an arbitrary layer, Based on this, the light absorption coefficient of an arbitrary layer can be selectively calculated. Since the equivalent scattering coefficient is taken into account when calculating the light absorption coefficient, the calculation result of the light absorption coefficient is highly accurate. Therefore, by calculating the concentration of the target component based on the calculated light absorption coefficient, it is possible to reduce the influence of noise due to other layers and perform highly accurate concentration quantification.

In some embodiments of the present invention, the observation target has a laminated structure of n layers or more, and an equivalent scattering coefficient of a light propagation path of light received by the first light receiving unit or the second light receiving unit is expressed as μ _s ′. (T), the equivalent scattering coefficient of the m-th layer is μ _sm , the average optical path length of the m-th layer at time t is L _m ′ (t), the optical path length of the m-th layer at time t is L _m (t), When the light intensity at time t of the model of the time-resolved waveform of the short-time pulsed light is N (t), in the first step, the light intensity at least for a predetermined time τ1 to τ2 is acquired, The approximate solution of the equivalent scattering coefficient of each of the layers of the plurality of light scattering media is calculated from the following equation (2), and the model of the propagation optical path length distribution generated from the approximate solution of the equivalent scattering coefficient is calculated. Correction of optical path length of each layer of the plurality of light scattering media at a predetermined time And a correction value of the light intensity at the predetermined time of the model of the time-resolved waveform of the short-time pulse light, and the correction value of the optical path length and the correction value of the light intensity model are obtained as follows: Substituting into the equation (2), the correction value of the equivalent scattering coefficient of each of the plurality of light scattering medium layers is calculated as the equivalent scattering coefficient of each of the plurality of light scattering medium layers. It is characterized in that the equivalent scattering coefficient of the arbitrary layer is calculated by repeatedly performing until convergence to a true value.

  According to this method, when calculating the equivalent scattering coefficient, iterative calculation using the above equation (2) is performed until it converges to the true value of the equivalent scattering coefficient. Therefore, the equivalent scattering coefficient of an arbitrary layer can be calculated with high accuracy.

In some embodiments of the present invention, the observation target has a laminated structure of n layers or more, and the equivalent scattering coefficient of the light propagation path of the light received by the first light receiving means or the second light receiving means is expressed as μ _s ′ (t). , The equivalent scattering coefficient of the m-th layer is μ _sm , the average optical path length of the m-th layer at time t is L _m ′ (t), the optical path length of the m-th layer at time t is L _m (t), and the short-time pulse When the light intensity at time t of the model of the time-resolved waveform of light is N (t), the light intensity at least for a predetermined time τ1 to τ2 is acquired, and a plurality of light scatterings are obtained from the following equation (2). An approximate solution of the equivalent scattering coefficient of each layer of the medium is calculated, and the layers of the plurality of light scattering media at the time t of the propagation path length distribution model generated from the approximate solution of the equivalent scattering coefficient are calculated. The correction value of the optical path length of each layer and the model of the time-resolved waveform of the short-time pulsed light The light intensity correction value at the predetermined time is obtained, the optical path length correction value and the light intensity model correction value are substituted into the following equation (2), and the plurality of light scattering media: Repeatedly calculating the correction value of the equivalent scattering coefficient of each layer of the plurality of layers until the true value of the equivalent scattering coefficient of each layer of the plurality of light scattering media converges to the arbitrary layer. The equivalent scattering coefficient is calculated.

  According to this method, when calculating the equivalent scattering coefficient, iterative calculation using the above equation (2) is performed until it converges to the true value of the equivalent scattering coefficient. Therefore, the equivalent scattering coefficient of an arbitrary layer can be calculated with high accuracy.

  In some embodiments of the present invention, the concentration of the target component in the arbitrary layer is calculated based on the light absorption coefficient calculated in the second step.

  According to this method, by calculating the concentration of the target component based on the calculated light absorption coefficient, it is possible to reduce the influence of noise due to other layers and perform highly accurate concentration quantification.

  In some embodiments of the present invention, when the observation target is skin and the arbitrary layer is a dermis layer, the concentration of glucose contained in the dermis layer is quantified.

  According to this method, by calculating the concentration of glucose contained in the dermis layer based on the calculated light absorption coefficient, it is possible to reduce the influence of noise caused by other layers and to accurately determine the concentration of glucose. Can do.

  Further, according to some aspects of the present invention, there is provided a concentration quantification device that quantifies the concentration of a target component in an arbitrary layer among observation targets formed from a plurality of light scattering medium layers. Irradiating means for irradiating the light, first light receiving means for receiving the light back-scattered by the observation object, the short-time pulse light, receiving the light back-scattered by the observation object for the short-time pulse light, and the observation object A second light receiving means and an irradiating means arranged so that a distance from an irradiation position irradiated with the short-time pulse light to a position for receiving the light backscattered by the observation object is different from that of the first light receiving means; First light intensity acquisition means for acquiring the intensity of light received by the first light receiving means at a predetermined time after the time when the short time pulse light is applied, and the irradiation means receives the short time pulse light. Second light intensity acquisition means for acquiring the intensity of light received by the second light receiving means at a predetermined time after the shooting time, light intensity acquired by the first light intensity acquisition means and the second light intensity acquisition means The first equivalent scattering coefficient calculating means for calculating the equivalent scattering coefficient of the propagation optical path of the light received by the first light receiving means or the second light receiving means based on the light intensity acquired by the first light receiving means, and the first equivalent scattering coefficient calculation Optical path length distribution storage means for storing a model of propagation optical path length distribution in each of the layers of the plurality of light scattering media generated based on the equivalent scattering coefficient at an arbitrary time calculated by the means, the first equivalent Time-resolved waveform storage means for storing a model of the time-resolved waveform of the short-time pulsed light generated based on the equivalent scattering coefficient at an arbitrary time calculated by the scattering coefficient calculating means, and the optical path length distribution record From the optical path length acquisition means for acquiring the optical path length of each of the layers of the plurality of light scattering media at the predetermined time of the model of the propagation optical path length distribution, and from the time-resolved waveform storage means, Light intensity model acquisition means for acquiring the light intensity at the predetermined time of the time-resolved waveform model of the time pulse light, the first light intensity acquisition means or the second light intensity acquisition means, or the first light intensity acquisition Means and a light intensity acquired by a third light intensity acquisition unit different from the second light intensity acquisition unit, an optical path length of each of the layers of the plurality of light scattering media acquired by the optical path length acquisition unit, and A program for calculating a light absorption coefficient for operating as a light absorption coefficient calculation means for calculating a light absorption coefficient of the arbitrary layer based on the light intensity model acquired by the light intensity model acquisition means. is there.

  According to this program, the light intensity acquired by the first light intensity acquisition unit, the second light intensity acquisition unit, or the third light intensity acquisition unit, and each of the plurality of light scattering medium layers acquired by the optical path length acquisition unit Based on the optical path length of the layer and the light intensity model acquired by the light intensity model acquisition means, the light absorption coefficient of an arbitrary layer can be selectively calculated. Also, the model of the propagation optical path length distribution and the model of the time-resolved waveform to be observed are equivalently scattered at an arbitrary time based on the intensity of the backscattered light received by the two light receiving means of the first light receiving means and the second light receiving means. A method of generating by coefficients is adopted. Thereby, it is possible to suppress the occurrence of an error factor when calculating the light absorption coefficient of an arbitrary layer, and to calculate the light absorption coefficient of an arbitrary layer with high accuracy.

Further, according to some aspects of the present invention, the equivalent scattering coefficient of the propagation path of light received by the first light receiving unit or the second light receiving unit is μ _s ′ (t), and the speed of light in the scatterer is set. c, a distance from an irradiation position at which the observation target is irradiated with the short-time pulsed light to a position at which the first light receiving unit receives light backscattered by the observation target, ρ ₁ , and a distance from the irradiation position to the second The distance to the position where the light receiving means receives the light backscattered by the observation target is ρ ₂ , the light intensity acquired by the first light intensity acquisition means at time t is R (ρ ₁ , t), and the second light. When the light intensity acquired by the intensity acquisition unit at time t is R (ρ ₂ , t), the first equivalent scattering coefficient calculation unit calculates the first light receiving unit or the second unit from the following equation (1). Equivalent scattering of the propagation path of light received by the light receiving means It calculates the number, characterized in that.

  According to this program, the equivalent scattering coefficient at an arbitrary time is calculated by the above equation (1). Therefore, the equivalent scattering coefficient time function of the light propagation optical path can be calculated with high accuracy.

  Further, according to some aspects of the present invention, an optical path length of each of the layers of the plurality of light scattering media acquired by the optical path length acquisition unit, a light intensity model acquired by the light intensity model acquisition unit, Based on the above, the second equivalent scattering coefficient calculating means for calculating the equivalent scattering coefficient of the arbitrary layer is operated, and the light absorption coefficient calculating means is the first light intensity acquiring means or the second light intensity acquiring means. Alternatively, the light intensity acquired by the third light intensity acquisition unit, the optical path length of each of the layers of the plurality of light scattering media acquired by the optical path length acquisition unit, and the light intensity model acquisition unit acquired The light absorption coefficient of the arbitrary layer is calculated based on the light intensity model and the equivalent scattering coefficient of the arbitrary layer calculated by the second equivalent scattering coefficient calculation means.

  According to this program, the light intensity acquired by the first light intensity acquisition unit, the second light intensity acquisition unit, or the third light intensity acquisition unit, and each of the plurality of light scattering medium layers acquired by the optical path length acquisition unit The light absorption coefficient of an arbitrary layer based on the optical path length of the layer, the light intensity model acquired by the light intensity model acquisition means, and the equivalent scattering coefficient of the arbitrary layer calculated by the second equivalent scattering coefficient calculation means Can be calculated selectively. Since the equivalent scattering coefficient is taken into account when calculating the light absorption coefficient, the calculation result of the light absorption coefficient is highly accurate. Therefore, by calculating the concentration of the target component based on the calculated light absorption coefficient, it is possible to reduce the influence of noise due to other layers and perform highly accurate concentration quantification.

In some embodiments of the present invention, the observation target has a laminated structure of n layers or more, and an equivalent scattering coefficient of a light propagation path of light received by the first light receiving unit or the second light receiving unit is expressed as μ _s ′. (T), the equivalent scattering coefficient of the m-th layer is μ _sm , the average optical path length of the m-th layer at time t is L _m ′ (t), the optical path length of the m-th layer at time t is L _m (t), When the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light is N (t), the light intensity acquisition means acquires the light intensity at least for a predetermined time τ1 to τ2, The second equivalent scattering coefficient calculating means calculates an approximate solution of an equivalent scattering coefficient of each of the plurality of light scattering medium layers from the following equation (2), and is generated from the approximate solution of the equivalent scattering coefficient. The plurality of light scattering media at the predetermined time of the propagation optical path length distribution model A correction value of the optical path length of each layer of the quality layer and a correction value of the light intensity at the predetermined time of the time-resolved waveform model of the short-time pulsed light, and the correction value of the optical path length And calculating the correction value of the equivalent scattering coefficient of each of the layers of the plurality of light scattering media by substituting the correction value of the light intensity model and the correction value of the light intensity model into the following equation (2): It is characterized in that the equivalent scattering coefficient of the arbitrary layer is calculated by repeatedly performing until it converges to the true value of the equivalent scattering coefficient of each layer of the medium.

  According to this program, when calculating the equivalent scattering coefficient, iterative calculation is performed using the above equation (2) until it converges to the true value of the equivalent scattering coefficient. Therefore, the equivalent scattering coefficient of an arbitrary layer can be calculated with high accuracy.

  Further, according to some aspects of the present invention, a concentration for operating as a concentration calculating unit that calculates the concentration of the target component in the arbitrary layer based on the light absorption coefficient calculated by the light absorption coefficient calculating unit. This is a program that performs calculation.

  According to this program, by calculating the concentration of the target component based on the calculated light absorption coefficient, it is possible to reduce the influence of noise due to other layers and perform highly accurate concentration quantification.

  In some embodiments of the present invention, when the observation target is skin and the arbitrary layer is a dermis layer, the concentration of glucose contained in the dermis layer is quantified.

  According to this program, by calculating the concentration of glucose contained in the dermis layer based on the calculated light absorption coefficient, the influence of noise by other layers can be reduced, and the concentration of glucose can be determined with high accuracy. Can do.

It is a schematic block diagram which shows the structure of the blood glucose level measuring apparatus which concerns on 1st Embodiment of this invention. It is a graph which shows the propagation optical path length distribution of each layer which the simulation part computed. It is a graph which shows the time-resolved waveform which the simulation part computed. It is a graph which shows the absorption spectrum of the main component of skin. It is a flowchart which shows the operation | movement which the blood glucose level measuring apparatus which concerns on 1st Embodiment of this invention measures a blood glucose level. It is a flowchart which shows the operation | movement which the blood glucose level measuring apparatus which concerns on 2nd Embodiment of this invention measures a blood glucose level. It is a schematic block diagram which shows the structure of the blood glucose level measuring apparatus which concerns on 3rd Embodiment of this invention. It is a flowchart which shows the operation | movement which the blood glucose level measuring apparatus which concerns on 3rd Embodiment of this invention measures a blood glucose level.

  Embodiments of the present invention will be described below with reference to the drawings.

(First embodiment)
FIG. 1 is a schematic block diagram showing a configuration of a blood sugar level measuring apparatus according to the first embodiment of the present invention.
The blood glucose level measuring apparatus 100 (concentration determination apparatus) includes an irradiation unit 101 (irradiation unit), a first light receiving unit 102 (first light receiving unit), a second light receiving unit 103 (second light receiving unit), and first measurement light intensity acquisition. Unit 104 (first light intensity acquisition unit), second measurement light intensity acquisition unit 105 (second light intensity acquisition unit), first equivalent scattering coefficient calculation unit 106 (first equivalent scattering coefficient calculation unit), simulation unit 107, Optical path length distribution storage unit 108 (optical path length distribution storage unit), time-resolved waveform storage unit 109 (time-resolved waveform storage unit), optical path length acquisition unit 110 (optical path length acquisition unit), non-absorption light intensity acquisition unit 111 (light intensity) A model acquisition unit), a light absorption coefficient calculation unit 112 (light absorption coefficient calculation unit), a component absorption information storage unit 113, a concentration calculation unit 114 (concentration calculation unit), a concentration unit conversion unit 115, and a concentration display unit 116.

  The blood glucose level measuring apparatus 100 measures the concentration of glucose (target component) contained in the dermis layer (arbitrary layer) of the skin (observation target).

  The irradiation unit 101 irradiates the skin with short-time pulsed light. The plurality of short-time pulse lights emitted by the irradiation unit 101 is light having a wavelength at which the orthogonality of the absorption spectrum distribution of each component of the main component constituting the skin increases, that is, each of the main components constituting the skin. Among the components, the maximum value of the absorption spectrum of a specific component in a certain main component includes light having a wavelength that is significantly different from the maximum value of the absorption spectrum of another component.

The first light receiving unit 102 receives light obtained by back-scattering short-time pulsed light by the skin.
The second light receiving unit 103 receives light obtained by backscattering the short-time pulsed light by the skin. The second light receiving unit 103 is arranged such that the distance from the irradiation position where the pulsed light is irradiated to the skin for a short time to the position where the light backscattered by the skin is received is different from that of the first light receiving unit 102.

The first measurement light intensity acquisition unit 104 acquires the light intensity at a certain time of the light received by the first light receiving unit 102.
The second measurement light intensity acquisition unit 105 acquires the light intensity at a certain time when the light received by the second light receiving unit 103 is received.

  Based on the light intensity acquired by the first measurement light intensity acquisition unit 104 and the light intensity acquired by the second measurement light intensity acquisition unit 105, the first equivalent scattering coefficient calculation unit 106 The equivalent scattering coefficient of the propagation optical path of the light received by the light receiving unit 103 is calculated.

  Based on the equivalent scattering coefficient at an arbitrary time calculated by the first equivalent scattering coefficient calculation unit 106, the simulation unit 107 calculates a propagation optical path length distribution model of each layer of skin and a model of time-resolved waveform of short-time pulsed light. Generate. The simulation is performed using, for example, a Monte Carlo method.

The optical path length distribution storage unit 108 stores a model of the propagation optical path length distribution of each skin layer generated by the simulation unit 107.
The time-resolved waveform storage unit 109 stores a model of the time-resolved waveform of the short-time pulsed light generated by the simulation unit 107.

The optical path length acquisition unit 110 acquires the optical path length at a certain time from the optical path length distribution storage unit 108.
The non-absorption light intensity acquisition unit 111 acquires the light intensity at a certain time from the time-resolved waveform storage unit 109.

The light absorption coefficient calculation unit 112 calculates the light absorption coefficient in the dermis layer of the skin irradiated with the short-time pulse light.
The component absorption information storage unit 113 stores in advance the light absorption coefficient or molar absorption coefficient of the main component of the skin.

The concentration calculation unit 114 calculates the concentration of glucose contained in the dermis layer.
The concentration unit converter 115 converts the glucose concentration unit into a desired unit.
The concentration display unit 116 displays the glucose concentration.

  In the blood sugar level measuring apparatus 100 of the present embodiment, the irradiation unit 101 irradiates the skin with pulsed light for a short time. The first light receiving unit 102 receives light obtained by backscattering the short-time pulse light by the skin, and the first measurement light intensity acquisition unit 104 acquires the intensity of light received by the first light receiving unit 102 at time t. The second light receiving unit 103 receives light obtained by back-scattering the short-time pulsed light by the skin, and the second measurement light intensity acquisition unit 105 acquires the intensity of light received by the second light receiving unit 103 at time t. Next, the first equivalent scattering coefficient calculation unit 106 at an arbitrary time in the dermis layer based on the light intensity acquired by the first measurement light intensity acquisition unit 104 and the light intensity acquired by the second measurement light intensity acquisition unit 105. Calculate the equivalent scattering coefficient. Next, the simulation unit 107 generates a model of the propagation optical path length distribution of each layer of the skin and a model of the time-resolved waveform of the short-time pulsed light based on the equivalent scattering coefficient at an arbitrary time. The optical path length distribution storage unit 108 stores a model of the propagation optical path length distribution of each skin layer generated by the simulation unit 107. The time-resolved waveform storage unit 109 stores a model of the time-resolved waveform of the short-time pulse light generated by the simulation unit 107. The optical path length acquisition unit 110 acquires the optical path length of each layer of the skin at time t of the propagation optical path length distribution in the skin model from the optical path length distribution storage unit 108. The non-absorption light intensity acquisition unit 111 acquires the light intensity at time t of the time-resolved waveform of the short-time pulsed light in the skin model from the time-resolved waveform storage unit 109.

Next, the light absorption coefficient calculation unit 112 includes the light intensity acquired by the first measurement light intensity acquisition unit 104 or the second measurement light intensity acquisition unit 105, the optical path length of each layer of the skin acquired by the optical path length acquisition unit 110, and The light absorption coefficient of the dermis layer of the skin is calculated based on the light intensity acquired by the non-absorption light intensity acquisition unit 111. Then, the concentration calculation unit 114 calculates the glucose concentration in the dermis layer based on the light absorption coefficient calculated by the light absorption coefficient calculation unit 112.
The light intensity may be a light intensity acquired by a third measurement light intensity acquisition unit different from the first measurement light intensity acquisition unit 104 and the second measurement light intensity acquisition unit 105. In this case, it is desirable to arrange the third measurement light intensity acquisition unit between the first measurement light intensity acquisition unit 104 and the second measurement light intensity acquisition unit 105.

  Thereby, the influence of noise by layers other than the dermis layer can be reduced, and the concentration of glucose contained in the dermis layer can be calculated. The glucose concentration calculated by the concentration calculation unit 114 is converted into a desired unit by the concentration unit conversion unit 115 and displayed on the concentration display unit 116.

Next, the operation of the blood sugar level measuring apparatus 100 will be described.
The blood glucose level measuring apparatus 100 calculates the propagation optical path length distribution and the time-resolved waveform in each layer of the skin in advance before measuring the blood glucose level.

  By the way, as a method of calculating the propagation optical path length distribution and the time-resolved waveform, a skin model having general optical characteristics based on the light scattering coefficient, light absorption coefficient and thickness of each layer of the skin determined by taking a sample in advance. There is a method of calculating by generating a light and performing a simulation of irradiating the skin model with light. However, in the simulation using the skin model, there is a concern that a deviation from a general value due to individual differences or physical condition at the time of measurement may be an error factor when calculating the light absorption coefficient of the dermis layer of the skin.

  On the other hand, in this embodiment, the intensity of the backscattered light received by the two light receiving units, the first light receiving unit 102 and the second light receiving unit 103, of the skin propagation optical path length distribution model and the time-resolved waveform model. Based on the above, a method of generating with an equivalent scattering coefficient at an arbitrary time is adopted. This suppresses the occurrence of an error factor when calculating the light absorption coefficient of the dermis layer of the skin, and enables the light absorption coefficient of the dermis layer to be calculated with high accuracy.

  The simulation unit 107 generates a skin propagation optical path length distribution model and a time-resolved waveform model using the equivalent scattering coefficient at an arbitrary time calculated by the first equivalent scattering coefficient calculation unit 106. The light absorption coefficient of the skin used here is zero.

  The simulation unit 107 performs a simulation of irradiating the skin with light. At this time, it is necessary to determine the distance between the position of the irradiation unit 101 and the position of the first light receiving unit 102 and the distance between the position of the irradiation unit 101 and the position of the second light receiving unit 103. The first light receiving unit 102 and the second light receiving unit 103 are positioned so that the distances from the irradiation position where the pulsed light is applied to the skin for a short time to the position where the light backscattered by the skin is received are different from each other. . The simulation is preferably performed using the Monte Carlo method. The simulation by the Monte Carlo method is performed as follows, for example.

  First, the simulation unit 107 performs calculation to irradiate the skin with a photon (light beam) as a model of light to be irradiated. Photons irradiated on the skin move in the skin. At this time, the photon determines the distance L and the direction θ to the next advancing point by a random number R (0 ≦ R ≦ 1). The simulation unit 107 calculates the distance L to the point at which the photon advances next using the equation (10).

Here, ln (A) represents the natural logarithm of A. Μ _sm represents the scattering coefficient of the m-th layer of the skin (any one of the epidermis layer, dermis layer, and subcutaneous tissue layer).
In addition, the simulation unit 107 calculates the direction θ up to the next point where the photon travels according to equation (11).

However, g shows the anisotropic parameter which is the average of the cosine of a scattering angle, and the anisotropic parameter of skin is about 0.9.
The simulation unit 107 can calculate the photon movement path from the irradiation unit 101 to the first light receiving unit 102 by repeating the calculations of the above equations (10) and (11) every unit time. The simulation unit 107 calculates the movement distance for a plurality of photons. For example, the simulation unit 107 calculates the movement distance for 10 ⁸ photons.

FIG. 2 is a graph showing the propagation optical path length distribution of each layer (skin layer, dermis layer, subcutaneous tissue layer) calculated by the simulation unit. In the figure, as an example, the first light receiving unit 102 of the two light receiving units is used.
The horizontal axis of FIG. 2 shows the elapsed time from photon irradiation, and the vertical axis shows the logarithmic display of the optical path length. The simulation unit 107 classifies the movement path of each photon that has reached the first light receiving unit 102 for each layer through which the movement path passes. Then, the simulation unit 107 calculates the propagation path length distribution of each layer of the skin as shown in FIG. 2 by calculating the average length of the movement path of the photons that arrived per unit time for each classified layer.

FIG. 3 is a graph showing a time-resolved waveform calculated by the simulation unit. In the figure, as an example, the first light receiving unit 102 of the two light receiving units is used.
The horizontal axis in FIG. 3 indicates the elapsed time from the photon irradiation, and the vertical axis indicates the number of photons detected by the first light receiving unit 102. The simulation unit 107 calculates a time-resolved waveform as shown in FIG. 3 by calculating the number of photons that have reached the first light receiving unit 102 per unit time.
Through the processing described above, the simulation unit 107 calculates the propagation optical path length distribution and the time-resolved waveform for a plurality of wavelengths. At this time, the simulation unit 107 may calculate the propagation optical path length distribution and the time-resolved waveform with respect to the wavelength at which the orthogonality of the absorption spectrum of the skin main components (water, protein, lipid, glucose, etc.) becomes high.

FIG. 4 is a graph showing the absorption spectrum of the main component of the skin.
The horizontal axis in FIG. 4 indicates the wavelength of light to be irradiated, and the vertical axis indicates the light absorption coefficient. Referring to FIG. 4, the light absorption coefficient of glucose becomes maximum when the wavelength is 1600 nm, and the light absorption coefficient of water becomes maximum when the wavelength is 1450 nm. For this reason, the simulation unit 107 may calculate the propagation optical path length distribution and the time-resolved waveform with respect to a wavelength at which the orthogonality of the absorption spectrum of the main component of skin, such as 1450 nm and 1600 nm, becomes high.

Next, the operation in which the blood sugar level measuring apparatus 100 measures the blood sugar level will be described.
FIG. 5 is a flowchart showing the operation of the blood sugar level measuring apparatus according to the first embodiment for measuring the blood sugar level.
First, when the user places the blood glucose level measuring device 100 on the skin and operates the blood glucose level measuring device 100 by pressing a measurement start switch (not shown) or the like, the irradiation unit 101 has a short wavelength λ ₁ with respect to the skin. Time pulse light is irradiated (step S1). Here, the wavelength λ ₁ is _one of a plurality of wavelengths calculated by the simulation unit 107 for the propagation optical path length distribution and the time-resolved waveform.

  When the irradiation unit 101 irradiates the pulsed light for a short time, the first light receiving unit 102 and the second light receiving unit 103 receive the light irradiated from the irradiation unit 101 and back-scattered by the skin (step S2). At this time, the first light receiving unit 102 and the second light receiving unit 103 register the received light intensity for each unit time (for example, every 1 picosecond) from the start of irradiation in the internal memory.

When the first light receiving unit 102 completes the light reception, the first measurement light intensity acquisition unit 104 irradiates the light reception intensity R (ρ ₁ , t) at different times t stored in the internal memory of the first light receiving unit 102. It is acquired at a predetermined time resolution within a predetermined time from the start (step S3). That is, the first measurement light intensity acquisition unit 104 acquires the time characteristic of the received light intensity.
When the second light receiving unit 103 completes the light reception, the second measurement light intensity acquisition unit 105 irradiates the received light intensity R (ρ ₂ , t) at a different time t stored in the internal memory of the second light receiving unit 103. It is acquired at a predetermined time resolution within a predetermined time from the start (step S3). That is, the second measurement light intensity acquisition unit 105 acquires the time characteristic of the received light intensity.

When the measurement light intensity acquisition units 104 and 105 acquire the light intensity, the first equivalent scattering coefficient calculation unit 106 calculates the equivalent at an arbitrary time from a certain received light intensity R (ρ ₁ , t), R (ρ ₂ , t). A scattering coefficient is calculated (step S4).

In the present embodiment, the first equivalent scattering coefficient calculation unit 106 calculates an equivalent scattering coefficient at an arbitrary time from the following equation (12). However, the natural logarithm is ln (•), the equivalent scattering coefficient at an arbitrary time at an arbitrary time t is μ _s ′ (t), the light absorption coefficient is μ _a , the speed of light in the scatterer is c, The distance from the irradiation position where the observation target is irradiated with the short-time pulse light to the position where the first light receiving unit 102 receives the light backscattered by the observation target is ρ ₁ , and the second light receiving means 103 from the irradiation position depends on the observation target. The distance to the position for receiving the backscattered light is ρ ₂ , the light intensity acquired by the first light intensity acquisition unit 104 at time t is R (ρ ₁ , t), and the second light intensity acquisition unit 105 is at time t. Let the acquired light intensity be R (ρ ₂ , t).

Here, the derivation process of the equation (12) will be described.
The reflection-type impulse response R when the impulse light is incident on the scatterer is expressed by the diffusion approximate analytical solution of the transport equation (reference: MS, Patterson, B. Chance and BC, Wilson, “Time resolved reflectance and transmittance for the From noninvasive measurement of tissue optical properties, “Appl. Opt., 28, 12, 2331-6, 1989), the following equation (13) is given as a function of the distance ρ from the incident point and time t.

Here, c is the speed of light in the scatterer, μ _s is a scattering coefficient, μ _a is a light absorption coefficient, μ _s ′ is an equivalent scattering coefficient at an arbitrary time, and g is an anisotropic parameter. Therefore, the time-resolved waveforms R (ρ ₁ , t) and R (ρ ₂ , t) at different distances ρ1 and ρ2 are expressed by the following equations (14) and (15) from the above equation (13). Is done.

Here, when the ratio of the above-mentioned formulas (14) and (15) is taken, the following formula (16) is obtained. As a result, exp (−μ _a ct) that strongly expresses the influence of the light absorption coefficient μ _a can be eliminated.

In general, since the relationship of μ _a << μ _s ′ is established in living tissue, the equivalent scattering coefficient at an arbitrary time shown in the following equation (1) is estimated by modifying the above equation (16) with respect to μ _s ′. Get the formula.

  In this way, the above equation (12) is derived.

  Note that the equivalent scattering coefficient at an arbitrary time can also be expressed as the following expression (17) using the scattering coefficient.

  Here, g is an anisotropic parameter. g is an index indicating the directionality of scattering. g takes a value between -1 and 1, with 1 indicating complete forward scattering and -1 indicating complete backscattering. In the case of 0, isotropic scattering is indicated, and the equivalent scattering coefficient and the scattering coefficient at an arbitrary time are equal.

  Scattering that occurs in living tissue is strong forward scattering with g = 0.9, but by repeating the scattering many times in the tissue, a state similar to isotropic scattering is observed as a result. . Therefore, the scattering coefficient when it is regarded as isotropic scattering becomes an equivalent scattering coefficient at an arbitrary time. It can be said that the equivalent scattering coefficient at an arbitrary time represents how many scattering coefficients correspond when scattering is considered as isotropic scattering. For example, when g = 0.9, it can be regarded as isotropic scattering with a scattering coefficient of 1/10.

  Returning to FIG. 5, when the first equivalent scattering coefficient calculation unit 106 calculates the equivalent scattering coefficient at an arbitrary time, the simulation unit 107 models the propagation optical path length distribution of each layer of the skin based on the equivalent scattering coefficient at the arbitrary time. A model of a time-resolved waveform of short-time pulse light is generated.

  The optical path length distribution storage unit 108 stores a model of the propagation optical path length distribution of each skin layer generated by the simulation unit 107. The time-resolved waveform storage unit 109 stores a model of the time-resolved waveform of the short-time pulse light generated by the simulation unit 107.

Optical path length obtaining unit 110, the optical path length distribution storage unit 108, the optical path length of each layer of the skin at time _{t 1 ~t 3 L 1 (t} 1) ~L 1 (t 3), L 2 (t 1) ~L ₂ (t ₃ ), L ₃ (t ₁ ) to L ₃ (t ₃ ) are acquired (step S5).

Further, the non-absorption light intensity acquisition unit 111 acquires the numbers of detected photons N (t ₁ ) to N (t ₃ ) at times t _{1 to} t ₃ from the time-resolved waveform storage unit 109 (step S6).

When the optical path length acquisition unit 110 acquires the optical path length of each layer of the skin and the non-absorption light intensity acquisition unit 111 acquires the number of detected photons, the light absorption coefficient calculation unit 112 calculates the skin based on the following equation (3): The light absorption coefficient of each layer is calculated (step S7).
However, the natural logarithm is ln (·), the light intensity at time t of the time-resolved waveform model of the short-time pulsed light is N (t), and the light intensity received by the light receiving means at time t is R (t), The optical absorption coefficient of the m-th layer is μ _am , the optical path length of the m-th layer at time t in the model of the propagation optical path length distribution is L _m (t), the number of incident photons is N _in , and the incident light intensity is I _in . .

  In addition, said (3) Formula is a general formula. When the expression (3) is modified so as to be applied to the three-layer structure in the present embodiment, the following expression (18) is obtained.

The light absorption coefficient calculation unit 112 calculates the light absorption coefficients μ _{a1 to} μ _a3 of each layer of the skin based on the expression (18) in which the expression (3) is applied to the three-layer structure of the present embodiment (step S7). . Here, the light absorption coefficient μ _a1 represents the light absorption coefficient of the epidermis layer, the light absorption coefficient μ _a2 represents the light absorption coefficient of the dermis layer, and the light absorption coefficient μ _a3 represents the light absorption coefficient of the subcutaneous tissue layer. Show.

Here, ln (A) represents the natural logarithm of A. I _in indicates the light intensity of the short-time pulse light irradiated by the irradiation unit 101. N _in indicates the number of photons on which the simulation unit 107 has simulated irradiation.

When the light absorption coefficient calculation unit 112 calculates the light absorption coefficients μ _{a1 to} μ _a3 of each layer of the skin, the light absorption coefficient calculation unit 112 calculates the light absorption coefficient μ for the same number of wavelengths as the number of main components of the skin. It determines whether to calculate the _{a1 ~μ a3} (step S8). In the present embodiment, since the blood sugar level is measured with four types of main components of the skin, water, protein, lipid, and glucose, the light absorption coefficient calculation unit 112 emits light with respect to four types of wavelengths λ _{1 to} λ ₄ . It is determined whether or not the absorption coefficients μ _{a1 to} μ _a3 are calculated. Here, the wavelengths λ _{1 to} λ ₄ are selected from a plurality of wavelengths calculated by the simulation unit 107 for the propagation optical path length distribution and the time-resolved waveform.

When the light absorption coefficient calculation unit 112 determines that there are wavelengths λ _{1 to} λ ₄ for which the light absorption coefficients μ _{a1 to} μ _a3 are not calculated (step S8: NO), the process returns to step S1 and still has the light absorption coefficient μ. and calculates the light absorption coefficient μ _a1 ~μ _a3 wavelength lambda ₁ to [lambda] _4, which is not calculated _{a1 ~μ a3.}

On the other hand, when the light absorption coefficient calculation unit 112 determines that the light absorption coefficients μ _{a1 to} μ _a3 of the wavelengths λ _{1 to} λ ₄ are calculated (step S8: YES), the concentration calculation unit 114 calculates the following formula: Based on (5), the concentration of glucose contained in the dermis is calculated (step S9).

Here, the light absorption coefficient in the m-th layer is μ _am , the light absorption coefficient of the i-th component forming the skin is μ _ai , and the volume concentration of the i-th component forming the skin is c _vi .
The above formula (5) is a general formula. When the equation (5) is modified to apply to the four wavelengths in the present embodiment, the following equation (19) is obtained.

However, μ _a2 (λ) is the optical absorption coefficient of the wavelength lambda ₁ to [lambda] ₄ in the dermis layer, μ _aw (λ) is the optical absorption coefficient of water in the wavelength lambda ₁ to [lambda] ₄ in the dermis layer, μ _ap (λ) is The light absorption coefficient of the protein with wavelengths λ _{1 to} λ ₄ in the dermis layer, μ _al (λ) is the light absorption coefficient of the lipid with wavelengths λ _{1 to} λ ₄ in the dermis layer, and μ _ag (λ) is the wavelength λ ₁ in the dermis layer. The light absorption coefficient of glucose of ˜λ ₄ is shown. C _vw is the volume concentration of water (volume fraction), c _vp is the volume concentration of protein (volume fraction), c _vl is the volume concentration of lipid (volume fraction), and c _vg is the volume concentration of volume (volume). Fraction).

The concentration calculation unit 114 calculates glucose from the light absorption coefficient of the main component in the measurement target stored in the component absorption information storage unit 113 and the light absorption coefficient μ _a2 in the dermis layer calculated by the above equation (19). The concentration of is calculated.

  The glucose concentration may be calculated using the following equation (6) instead of the above equation (5).

However, the light absorption coefficient in the m-th layer is μ _am , the molar extinction coefficient of the i-th component forming the skin is ε _i , and the molar concentration of the i-th component forming the skin is c _i .
The above formula (6) is a general formula. When the equation (6) is modified to be applied to the three-layer structure in the present embodiment, the following equation (20) is obtained.

Where ε _w (λ) is the molar extinction coefficient of water of wavelengths λ _{1 to} λ ₄ in the dermis layer, ε _p (λ) is the molar extinction coefficient of protein of wavelengths λ _{1 to} λ ₄ in the dermis layer, and ε _l (λ ) Represents the molar extinction coefficient of lipids with wavelengths λ _{1 to} λ ₄ in the dermis layer, and ε _g (λ) represents the molar extinction coefficient of glucose with wavelengths λ _{1 to} λ ₄ in the dermis layer. Further, c _w represents molar concentration of water, c _p is the molar concentration of the protein, c _l is the molar concentration of the lipid, c _g is the molar concentration of glucose.

  The concentration calculation unit 114 calculates the glucose concentration from the molar extinction coefficient of the main component in the measurement target stored in the component absorption information storage unit 113 and the molar extinction coefficient ε in the dermis layer calculated by the above equation (20). Calculate the concentration.

  The concentration unit converter 115 converts the glucose concentration unit calculated by the concentration calculator 114 into a desired unit. The concentration display unit 116 displays the glucose concentration.

  As described above, according to this embodiment, the skin is irradiated with pulsed light for a short time, the intensity of the light received at a predetermined time, the optical path length of each layer at the predetermined time of the model of the propagation optical path length distribution, and the short The light absorption coefficient of the dermis layer can be selectively calculated based on the light intensity at a predetermined time of the time-resolved waveform model of the time pulse light. Therefore, by calculating the concentration of the target component based on the calculated light absorption coefficient, it is possible to reduce the influence of noise due to other layers and perform highly accurate concentration quantification.

  By the way, as a method of calculating the propagation optical path length distribution and the time-resolved waveform, a skin model having general optical characteristics based on the light scattering coefficient, light absorption coefficient and thickness of each layer of the skin determined by taking a sample in advance. There is a method of calculating by generating a light and performing a simulation of irradiating the skin model with light. However, in the simulation using the skin model, there is a concern that a deviation from a general value due to individual differences or physical condition at the time of measurement may be an error factor when calculating the light absorption coefficient of the dermis layer of the skin.

  On the other hand, in this embodiment, the intensity of the backscattered light received by the two light receiving units, the first light receiving unit 102 and the second light receiving unit 103, of the skin propagation optical path length distribution model and the time-resolved waveform model. Based on the above, a method of generating with an equivalent scattering coefficient at an arbitrary time is adopted. Therefore, it is possible to suppress the occurrence of an error factor when calculating the light absorption coefficient of the dermis layer of the skin, and to calculate the light absorption coefficient of the dermis layer with high accuracy.

  In the above embodiment, the backscattered light intensity N ′ (t) when the light absorption coefficient is zero and the number of incident photons is 1 can also be calculated using the following equation (21).

However, the natural logarithm is ln (·), the speed of light in the scatterer is c, and the first light receiving unit 102 receives the light backscattered by the observation target from the irradiation position where the observation target is irradiated with the short-time pulse light. Ρ ₁ , the distance from the irradiation position to the position where the second light receiving means 103 receives the light backscattered by the observation object, ρ ₂ , and the light acquired by the first light intensity acquisition unit 104 at time t Assume that the intensity is R (ρ ₁ , t), and the light intensity acquired by the second light intensity acquisition unit 105 at time t is R (ρ ₂ , t).

(Second Embodiment)
Next, a second embodiment of the present invention will be described in detail.
The second embodiment has the same configuration as the blood glucose level measuring apparatus 100 according to the first embodiment, and each measurement light intensity acquisition unit 104, 105, first equivalent scattering coefficient calculation unit 106, optical path length acquisition unit 110, none The operations of the absorption light intensity acquisition unit 111 and the light absorption coefficient calculation unit 112 are different.

FIG. 6 is a flowchart showing an operation in which the blood sugar level measuring apparatus according to the second embodiment measures the blood sugar level.
First, when operating the blood glucose measuring device 100, the irradiation unit 101 irradiates the short pulse light having a wavelength lambda ₁ to the skin (step S11). Here, the wavelength λ ₁ is _one of a plurality of wavelengths calculated by the simulation unit 107 for the propagation optical path length distribution and the time-resolved waveform.

  When the irradiation unit 101 emits the short-time pulse light, the first light receiving unit 102 and the second light receiving unit 103 receive the light emitted from the irradiation unit 101 and back-scattered by the skin (step S12). At this time, the first light receiving unit 102 and the second light receiving unit 103 register the received light intensity for each unit time (for example, every 1 picosecond) from the start of irradiation in the internal memory.

  When the first light receiving unit 102 completes the light reception, the first measurement light intensity acquisition unit 104 determines a predetermined time within a predetermined time from the start of irradiation based on the received light intensity stored in the internal memory of the first light receiving unit 102. The time distribution of the received light intensity is acquired with the resolution (step S13). When the second light receiving unit 103 completes the light reception, the second measurement light intensity acquisition unit 105 determines a predetermined time within a predetermined time from the start of irradiation based on the received light intensity stored in the internal memory of the second light receiving unit 103. The time distribution of the received light intensity is acquired with the resolution (step S13).

  When each of the measurement light intensity acquisition units 104 and 105 acquires the light intensity, the first equivalent scattering coefficient calculation unit 106 at a given time from the time distribution of the received light intensity with a predetermined time resolution within a predetermined time from the start of irradiation. An equivalent scattering coefficient is calculated (step S14).

  When the first equivalent scattering coefficient calculation unit 106 calculates an equivalent scattering coefficient at an arbitrary time, the simulation unit 107 calculates a propagation optical path length distribution model of each layer of skin based on the equivalent scattering coefficient at an arbitrary time, short-time pulse light. Generate a model of the time-resolved waveform.

  The optical path length distribution storage unit 108 stores a model of the propagation optical path length distribution of each skin layer generated by the simulation unit 107. The time-resolved waveform storage unit 109 stores a model of the time-resolved waveform of the short-time pulse light generated by the simulation unit 107.

The optical path length acquisition unit 110 acquires the optical path lengths L _{1 to} L ₃ of each layer of the skin during a certain time τ 1 to τ 2 from the propagation optical path length distribution of the wavelength λ ₁ stored in the optical path length distribution storage unit 108 (step) S15).

Further, no absorption at the light intensity acquisition unit 111, a time-resolved waveform of the wavelength lambda ₁ for storing the time-resolved waveform storage unit 109, acquires the detection number of photons during a time Tau1～tau2 (step S16).

When the optical path length acquisition unit 110 acquires the optical path length of each layer of the skin and the non-absorption light intensity acquisition unit 111 acquires the number of detected photons, the light absorption coefficient calculation unit 112 calculates the skin based on the following equation (4): The light absorption coefficient of each layer is calculated (step S17). However, the natural logarithm is ln (·), the light intensity at time t of the model of the time-resolved waveform of the short-time pulse light is N (t), and the light intensity acquired by the light intensity acquisition unit at time t is R (t), The light absorption coefficient of the m-th layer is μ _am , the optical path length of the m-th layer at time t in the propagation optical path length distribution model is L _m (t), the number of incident photons is N _in , and the incident light intensity is I _in .

  The above expression (4) is an expression obtained by developing the expression (3) used in the first embodiment into an integral type.

The light absorption coefficient calculation unit 112 calculates the light absorption coefficients μ _{a1 to} μ _a3 of each layer of the skin based on the equation (4) (step S17). Here, the light absorption coefficient μ _a1 represents the light absorption coefficient of the epidermis layer, the light absorption coefficient μ _a2 represents the light absorption coefficient of the dermis layer, and the light absorption coefficient μ _a3 represents the light absorption coefficient of the subcutaneous tissue layer.

Here, ln (A) represents the natural logarithm of A. I _in indicates the light intensity of the short-time pulse light irradiated by the irradiation unit 101. N _in indicates the number of photons on which the simulation unit 107 has simulated irradiation.

When the light absorption coefficient calculation unit 112 calculates the light absorption coefficients μ _{a1 to} μ _a3 of each layer of the skin, the light absorption coefficient calculation unit 112 calculates the light absorption coefficient μ for the same number of wavelengths as the number of main components of the skin. It determines whether to calculate the _{a1 ~μ a3} (step S18). In the present embodiment, since the blood sugar level is measured with four types of main components of the skin, water, protein, lipid, and glucose, the light absorption coefficient calculation unit 112 emits light with respect to four types of wavelengths λ _{1 to} λ ₄ . It is determined whether or not the absorption coefficients μ _{a1 to} μ _a3 are calculated. Here, the wavelengths λ _{1 to} λ ₄ are selected from a plurality of wavelengths calculated by the simulation unit 107 for the propagation optical path length distribution and the time-resolved waveform.

When the light absorption coefficient calculating unit 112 determines that there are wavelengths λ _{1 to} λ ₄ for which the light absorption coefficients μ _{a1 to} μ _a3 are not calculated (step S18: NO), the process returns to step S1 and still has the light absorption coefficient μ. and calculates the light absorption coefficient μ _a1 ~μ _a3 wavelength lambda ₁ to [lambda] _4, which is not calculated _{a1 ~μ a3.}

On the other hand, when the light absorption coefficient calculation unit 112 determines that the light absorption coefficients μ _{a1 to} μ _a3 of the wavelengths λ _{1 to} λ ₄ are calculated (step S18: YES), the concentration calculation unit 114 calculates the above formula. Based on the above equation (19) in which (5) is applied to the four wavelengths in this embodiment, the concentration of glucose contained in the dermis is calculated (step S19).

The concentration calculation unit 114 calculates glucose from the light absorption coefficient of the main component in the measurement target stored in the component absorption information storage unit 113 and the light absorption coefficient μ _a2 in the dermis layer calculated by the above equation (19). The concentration of is calculated.

  The concentration calculation unit 114 is based on the molar extinction coefficient of the main component in the measurement object stored in the component absorption information storage unit 113 and the molar extinction coefficient ε in the dermis layer calculated by the above equation (20). The concentration of glucose may be calculated.

  The concentration unit converter 115 converts the glucose concentration unit calculated by the concentration calculator 114 into a desired unit. The concentration display unit 116 displays the glucose concentration.

  As described above, also in this embodiment, by calculating the concentration of the target component based on the calculated light absorption coefficient, it is possible to reduce the influence of noise by other layers and perform highly accurate concentration quantification. . Further, it is possible to suppress the occurrence of an error factor when calculating the light absorption coefficient of the dermis layer of the skin, and to calculate the light absorption coefficient of the dermis layer with high accuracy.

  Further, according to the present embodiment, since the light absorption coefficient is calculated by the integral value of the optical path length during the time τ1 to τ2, the influence on the calculation result of the light absorption coefficient due to the error included in the measured light reception intensity is reduced. can do.

  In the above embodiment, the backscattered light intensity N ′ (t) when the light absorption coefficient is zero and the number of incident photons is 1 can also be calculated using the following equation (21).

However, the natural logarithm is ln (·), the speed of light in the scatterer is c, and the first light receiving unit 102 receives the light backscattered by the observation target from the irradiation position where the observation target is irradiated with the short-time pulse light. Ρ ₁ , the distance from the irradiation position to the position where the second light receiving means 103 receives the light backscattered by the observation object, ρ ₂ , and the light acquired by the first light intensity acquisition unit 104 at time t Assume that the intensity is R (ρ ₁ , t), and the light intensity acquired by the second light intensity acquisition unit 105 at time t is R (ρ ₂ , t).

(Third embodiment)
Next, a third embodiment of the present invention will be described in detail.
The blood sugar level measuring apparatus 200 according to the third embodiment has the same basic configuration as that of the blood sugar level measuring apparatus 100 according to the first embodiment, and further includes a second equivalent scattering coefficient calculating unit 117. Since other configurations are the same as those of the first embodiment, detailed description thereof is omitted.

FIG. 7 is a schematic block diagram showing a configuration of a blood sugar level measuring apparatus according to the third embodiment of the present invention.
The blood glucose level measuring apparatus 200 (concentration determination apparatus) includes an irradiation unit 101 (irradiation unit), a first light receiving unit 102 (first light receiving unit), a second light receiving unit 103 (second light receiving unit), and first measurement light intensity acquisition. Unit 104 (first light intensity acquisition unit), second measurement light intensity acquisition unit 105 (second light intensity acquisition unit), first equivalent scattering coefficient calculation unit 106 (first equivalent scattering coefficient calculation unit), simulation unit 107, Optical path length distribution storage unit 108 (optical path length distribution storage unit), time-resolved waveform storage unit 109 (time-resolved waveform storage unit), optical path length acquisition unit 110 (optical path length acquisition unit), non-absorption light intensity acquisition unit 111 (light intensity) Model acquisition unit), second equivalent scattering coefficient calculation unit 117 (second equivalent scattering coefficient calculation unit), light absorption coefficient calculation unit 112 (light absorption coefficient calculation unit), component absorption information storage unit 113, concentration calculation unit 114 (concentration) Calculation means) Comprising a density units conversion unit 115, density display section 116.

  The second equivalent scattering coefficient calculation unit 117 calculates the equivalent scattering of an arbitrary layer based on the optical path length of each skin layer acquired by the optical path length acquisition unit 110 and the light intensity acquired by the non-absorption light intensity acquisition unit 111. Calculate the coefficient.

In the present embodiment, the light absorption coefficient calculation unit 112 includes the light intensity acquired by the first measurement light intensity acquisition unit 104 or the second measurement light intensity acquisition unit 105, and the optical path of each layer of the skin acquired by the optical path length acquisition unit 110. Based on the length, the light intensity acquired by the non-absorption light intensity acquisition unit 111, and the equivalent scattering coefficient of an arbitrary layer calculated by the second equivalent scattering coefficient calculation unit 117, the light absorption coefficient of the dermis layer of the skin is calculated. calculate. Then, the concentration calculation unit 114 calculates the glucose concentration in the dermis layer based on the light absorption coefficient calculated by the light absorption coefficient calculation unit 112.
The light intensity may be a light intensity acquired by a third measurement light intensity acquisition unit different from the first measurement light intensity acquisition unit 104 and the second measurement light intensity acquisition unit 105. In this case, it is desirable to arrange the third measurement light intensity acquisition unit between the first measurement light intensity acquisition unit 104 and the second measurement light intensity acquisition unit 105.

Next, the operation in which the blood sugar level measuring apparatus 200 measures the blood sugar level will be described.
FIG. 8 is a flowchart showing the operation of the blood sugar level measuring apparatus according to the third embodiment for measuring the blood sugar level.
First, when the user places the blood sugar level measuring device 200 on the skin and operates the blood sugar level measuring device 200 by pressing a measurement start switch (not shown) or the like, the irradiation unit 101 has a short wavelength λ ₁ with respect to the skin. The time pulse light is irradiated (step S21). Here, the wavelength λ ₁ is _one of a plurality of wavelengths calculated by the simulation unit 107 for the propagation optical path length distribution and the time-resolved waveform.

  When the irradiation unit 101 irradiates the pulsed light for a short time, the first light receiving unit 102 and the second light receiving unit 103 receive the light irradiated from the irradiation unit 101 and back-scattered by the skin (step S22). At this time, the first light receiving unit 102 and the second light receiving unit 103 register the received light intensity for each unit time (for example, every 1 picosecond) from the start of irradiation in the internal memory.

When the first light receiving unit 102 completes the light reception, the first measurement light intensity acquisition unit 104 irradiates the light reception intensity R (ρ ₁ , t) at different times t stored in the internal memory of the first light receiving unit 102. Obtained at a predetermined time resolution within a predetermined time from the start (step S23). That is, the first measurement light intensity acquisition unit 104 acquires the time characteristic of the received light intensity.
When the second light receiving unit 103 completes the light reception, the second measurement light intensity acquisition unit 105 irradiates the received light intensity R (ρ ₂ , t) at a different time t stored in the internal memory of the second light receiving unit 103. Obtained at a predetermined time resolution within a predetermined time from the start (step S23). That is, the second measurement light intensity acquisition unit 105 acquires the time characteristic of the received light intensity.

When the measurement light intensity acquisition units 104 and 105 acquire the light intensity, the first equivalent scattering coefficient calculation unit 106 calculates the equivalent at an arbitrary time from a certain received light intensity R (ρ ₁ , t), R (ρ ₂ , t). A scattering coefficient is calculated (step S24). The first equivalent scattering coefficient calculation unit 106 calculates an equivalent scattering coefficient at an arbitrary time from the above equation (12).

  When the first equivalent scattering coefficient calculation unit 106 calculates an equivalent scattering coefficient at an arbitrary time, the simulation unit 107 calculates a propagation optical path length distribution model of each layer of skin based on the equivalent scattering coefficient at an arbitrary time, short-time pulse light. Generate a model of the time-resolved waveform.

  The optical path length distribution storage unit 108 stores a model of the propagation optical path length distribution of each skin layer generated by the simulation unit 107. The time-resolved waveform storage unit 109 stores a model of the time-resolved waveform of the short-time pulse light generated by the simulation unit 107.

The optical path length acquisition unit 110 acquires the optical path lengths L _{1 to} L ₃ of each layer of the skin during a certain time τ 1 to τ 2 from the propagation optical path length distribution of the wavelength λ ₁ stored in the optical path length distribution storage unit 108 (step) S25).

Further, no absorption at the light intensity acquisition unit 111, a time-resolved waveform of the wavelength lambda ₁ for storing the time-resolved waveform storage unit 109, acquires the detection number of photons during a time Tau1～tau2 (step S26).

  When the optical path length acquisition unit 110 acquires the optical path length of each layer of the skin and the non-absorbing light intensity acquisition unit 111 acquires the number of detected photons, the second equivalent scattering coefficient calculation unit 117 calculates the equivalent scattering coefficient of any layer of the skin Is calculated (step S27).

In the present embodiment, the second equivalent scattering coefficient calculation unit 117 first calculates an approximate solution of the equivalent scattering coefficient of each layer of the skin from the following equation (2). Next, based on the approximate solution of the equivalent scattering coefficient, the simulation unit 107 corrects the optical path length of each layer of the skin at a predetermined time of the propagation optical path length distribution model and the model of the time-resolved waveform of the short-time pulse light. The correction value of the light intensity at a predetermined time is generated. Then, by substituting the correction value of the optical path length and the correction value of the light intensity model into the following equation (2), calculating the correction value of the equivalent scattering coefficient of each layer of the skin is equivalent scattering of each layer of the skin Repeat until it converges to the true value of the coefficient. Thereby, the equivalent scattering coefficient of an arbitrary layer is calculated. However, the equivalent scattering coefficient at an arbitrary time at an arbitrary layer time t is μ _s ′ (t), the equivalent scattering coefficient at the m-th layer is μ _sm ′, and the average optical path length of the m-th layer at the time t is L _m ′. (T), the optical path length of the m-th layer at time t is L _m (t), and the light intensity at time t of the time-resolved waveform model of the short-time pulsed light is N (t).

Here, the process of deriving the above equation (2) will be described.
Consider the target scatterer divided into arbitrary n layers in the depth direction. If the equivalent scattering coefficient of each layer is μ _sm '(m = 1, 2,... N), μ _s ′ (t) obtained by the above equation (1) has an influence of the equivalent scattering coefficient of each layer. Should be received according to the weight. The weight is considered to depend on the optical path length through which the photon passes through each layer. Therefore, μ _s ′ (t) obtained by the above equation (1) can be approximated by the following equation (22) using the average optical path length L _m ′ (t) of the _mth layer of each photon. Conceivable.

Further, in order to reduce noise, when L _m ′ (t) is applied to both sides of the above equation (22) and time t is integrated from τ1 to τ2, the following equation (2) is obtained.

  In this way, equation (2) is obtained.

  Returning to FIG. 8, the calculation of the correction value of the equivalent scattering coefficient of each layer of the skin is repeated. Specifically, the second equivalent scattering coefficient calculation unit 117 calculates an approximate solution of the equivalent scattering coefficient of each layer of skin from the above equation (2), and the simulation unit 107 calculates the approximate solution of the equivalent scattering coefficient based on the approximate solution of the equivalent scattering coefficient. The correction value of the optical path length of each layer of the skin at a predetermined time of the generated propagation optical path length distribution model and the correction value of the light intensity at the predetermined time of the time-resolved waveform model of the short-time pulsed light are (2 Substituting into the formula, the correction value of the equivalent scattering coefficient of each layer of the skin is calculated. The calculation of the correction value is repeated until it converges to the true value of the equivalent scattering coefficient of each skin layer (step S28).

  Note that the number of repetitions may be repeated until the amount of change between the previous calculated value (for example, the primary correction value) and the current calculated value (for example, the secondary correction value) falls below a certain amount. Further, the number of repetitions may be set in advance.

Here, using the above equation (2), a description will be given of the abort determination when iteratively calculating.
In the estimation of the equivalent scattering coefficient, it is preferable to change the judgment of convergence each time depending on the degree of accuracy (how many decimal places are necessary).
A specific example will be given of the case where the obtained equivalent scattering coefficient is further used for calculating the light absorption coefficient and the concentration of the target component.
Assuming application to blood glucose level measurement and measurement, considering a simple aqueous glucose solution, it is necessary to obtain the light absorption coefficient on the order of 0.00001 / mm.
For example, consider a case where the light absorption coefficient is obtained using the following equation (23) in which the equation (1) of the patent document (Japanese Patent Application Laid-Open No. 2010-237139) is applied to a uniform model. By substituting N (t) and L ₁ (t) calculated by the convergence calculation for obtaining the equivalent scattering coefficient into the following (23), μ _a1 is obtained. Therefore, regarding the decision to abort when _performing repeated calculation, if the number of the fifth decimal place of μ _a1 of the calculation result does not vary over several to 10 times of the repeated calculation, the result converges within the required range. It can be judged that

  Returning to FIG. 8, when it is determined that the true value of the equivalent scattering coefficient of each layer of the skin has not converged (step S28: NO), the process returns to step S25, and the optical path length of each layer of the skin is acquired.

On the other hand, when it determines with having converged on the true value of the equivalent scattering coefficient of each layer of skin (step S28: YES), the light absorption coefficient calculation part 112 is light absorption of each layer of skin based on said (4) Formula. The coefficients μ _{a1 to} μ _a3 are calculated (step S29). Here, the light absorption coefficient μ _a1 represents the light absorption coefficient of the epidermis layer, the light absorption coefficient μ _a2 represents the light absorption coefficient of the dermis layer, and the light absorption coefficient μ _a3 represents the light absorption coefficient of the subcutaneous tissue layer. Show.

Here, ln (A) represents the natural logarithm of A. I _in indicates the light intensity of the short-time pulse light irradiated by the irradiation unit 101. N _in indicates the number of photons on which the simulation unit 107 has simulated irradiation.

When the light absorption coefficient calculation unit 112 calculates the light absorption coefficients μ _{a1 to} μ _a3 of each layer of the skin, the light absorption coefficient calculation unit 112 calculates the light absorption coefficient μ for the same number of wavelengths as the number of main components of the skin. It determines whether to calculate the _{a1 ~μ a3} (step S30). In the present embodiment, since the blood sugar level is measured with four types of main components of the skin, water, protein, lipid, and glucose, the light absorption coefficient calculation unit 112 emits light with respect to four types of wavelengths λ _{1 to} λ ₄ . It is determined whether or not the absorption coefficients μ _{a1 to} μ _a3 are calculated. Here, the wavelengths λ _{1 to} λ ₄ are selected from a plurality of wavelengths calculated by the simulation unit 107 for the propagation optical path length distribution and the time-resolved waveform.

When the light absorption coefficient calculating unit 112 determines that there are wavelengths λ _{1 to} λ ₄ for which the light absorption coefficients μ _{a1 to} μ _a3 are not calculated (step S30: NO), the process returns to step S1, and the light absorption coefficient μ is still present. and calculates the light absorption coefficient μ _a1 ~μ _a3 wavelength lambda ₁ to [lambda] _4, which is not calculated _{a1 ~μ a3.}

On the other hand, when it is determined that the light absorption coefficient calculation unit 112 calculates the light absorption coefficients μ _{a1 to} μ _a3 of the wavelengths λ _{1 to} λ ₄ (step S30: YES), the concentration calculation unit 114 19) The concentration of glucose contained in the dermis is calculated based on the equation (step S31).

The concentration calculation unit 114 calculates glucose from the light absorption coefficient of the main component in the measurement target stored in the component absorption information storage unit 113 and the light absorption coefficient μ _a2 in the dermis layer calculated by the above equation (19). The concentration of is calculated.

  The concentration calculation unit 114 is based on the molar extinction coefficient of the main component in the measurement object stored in the component absorption information storage unit 113 and the molar extinction coefficient ε in the dermis layer calculated by the above equation (20). The concentration of glucose may be calculated.

  The concentration unit converter 115 converts the glucose concentration unit calculated by the concentration calculator 114 into a desired unit. The concentration display unit 116 displays the glucose concentration.

  Thus, according to the present embodiment, the light intensity acquired by the first light intensity acquisition unit 104, the second light intensity acquisition unit 105, or the third light intensity acquisition unit, and the skin acquired by the optical path length acquisition unit 110. Based on the optical path length of each layer, the light intensity model acquired by the non-absorbing light intensity acquisition unit 111, and the equivalent scattering coefficient of the arbitrary layer calculated by the second equivalent scattering coefficient calculation unit 117. The light absorption coefficient can be selectively calculated. Since the equivalent scattering coefficient is taken into account when calculating the light absorption coefficient, the calculation result of the light absorption coefficient is highly accurate. Therefore, by calculating the concentration of the target component based on the calculated light absorption coefficient, it is possible to reduce the influence of noise due to other layers and perform highly accurate concentration quantification.

  Further, according to the present embodiment, when calculating the equivalent scattering coefficient, iterative calculation using the above equation (2) is performed until it converges to the true value of the equivalent scattering coefficient. Therefore, the equivalent scattering coefficient of an arbitrary layer can be calculated with high accuracy.

As described above, the embodiment of the present invention has been described in detail with reference to the drawings. However, the specific configuration is not limited to the above, and various design changes and the like can be made without departing from the scope of the present invention. It is possible to
For example, in the first embodiment and the second embodiment, the case where the concentration determination method is implemented in the blood glucose level measurement device 100 and the concentration of glucose contained in the dermis layer of the skin is measured has been described. The concentration determination method may be used for another apparatus for determining the concentration of a target component in an arbitrary observation target layer formed from a plurality of light scattering medium layers.

  The blood sugar level measuring apparatus 100 described above has a computer system inside. The operation of each processing unit described above is stored in a computer-readable recording medium in the form of a program, and the above processing is performed by the computer reading and executing this program. Here, the computer-readable recording medium means a magnetic disk, a magneto-optical disk, a CD-ROM, a DVD-ROM, a semiconductor memory, or the like. Alternatively, the computer program may be distributed to the computer via a communication line, and the computer that has received the distribution may execute the program.

The program may be for realizing a part of the functions described above.
Furthermore, what can implement | achieve the function mentioned above in combination with the program already recorded on the computer system, and what is called a difference file (difference program) may be sufficient.

DESCRIPTION OF SYMBOLS 100,200 ... Blood glucose level measuring apparatus (concentration determination apparatus), 101 ... Irradiation part (irradiation means), 102 ... First light receiving part (first light receiving part), 103 ... Second light receiving part (second light receiving part), 104 ... 1st measurement light intensity acquisition part (1st light intensity acquisition means), 105 ... 2nd measurement light intensity acquisition part (2nd light intensity acquisition means), 106 ... 1st equivalent scattering coefficient calculation part (1st equivalent scattering coefficient) Calculation means), 107 ... Simulation section, 108 ... Optical path length distribution storage section (optical path length distribution storage means), 109 ... Time-resolved waveform storage section (time-resolved waveform storage means), 110 ... Optical path length acquisition section (optical path length acquisition) Means), 111 ... Non-absorption light intensity acquisition part (light intensity model acquisition means), 112 ... Light absorption coefficient calculation part (light absorption coefficient calculation means), 114 ... Concentration calculation part (concentration calculation means), 115 ... Concentration unit conversion Part, 116... Density display part, 1 7 ... second scattering coefficient calculation unit (second scattering coefficient calculation means)

Claims (23)

A concentration quantification device for quantifying the concentration of a target component in an arbitrary layer among observation targets formed from a plurality of light scattering medium layers,
Irradiating means for irradiating the observation object with short-time pulsed light;
First light receiving means for receiving the light back-scattered by the observation object by the short-time pulse light;
The distance from the irradiation position at which the short-time pulsed light is back-scattered by the observation target and the position at which the short-time pulsed light is irradiated to the observation target to the position at which the back-scattered light is received by the observation target A second light receiving means arranged different from the first light receiving means,
First light intensity obtaining means for obtaining the intensity of light received by the first light receiving means at a predetermined time after the time when the irradiating means radiated pulsed light for a short time;
Second light intensity acquisition means for acquiring the intensity of the light received by the second light receiving means at a predetermined time after the time when the irradiation means irradiates the pulsed light for a short time;
Based on the light intensity acquired by the first light intensity acquisition means and the light intensity acquired by the second light intensity acquisition means, the equivalent of the propagation optical path of the light received by the first light receiving means or the second light receiving means First equivalent scattering coefficient calculating means for calculating a scattering coefficient;
An optical path length distribution storing a propagation optical path length distribution model in each of the layers of the plurality of light scattering media generated based on the equivalent scattering coefficient at an arbitrary time calculated by the first equivalent scattering coefficient calculating means. Storage means;
Time-resolved waveform storage means for storing a model of the time-resolved waveform of the short-time pulsed light generated based on the equivalent scattering coefficient at an arbitrary time calculated by the first equivalent scattering coefficient calculating means;
An optical path length acquisition means for acquiring an optical path length of each of the layers of the plurality of light scattering media at the predetermined time of the model of the propagation optical path length distribution from the optical path length distribution storage means;
A light intensity model acquisition means for acquiring the light intensity at the predetermined time of the time-resolved waveform model of the short-time pulsed light from the time-resolved waveform storage means;
The light intensity acquired by the first light intensity acquisition means, the second light intensity acquisition means, or a third light intensity acquisition means different from the first light intensity acquisition means and the second light intensity acquisition means, and the optical path Based on the optical path length of each of the layers of the plurality of light scattering media acquired by the length acquisition unit and the light intensity model acquired by the light intensity model acquisition unit, the light absorption coefficient of the arbitrary layer is calculated. A light absorption coefficient calculating means for calculating;
Based on the light absorption coefficient calculated by the light absorption coefficient calculation means, a concentration calculation means for calculating the concentration of the target component in the arbitrary layer;
Concentration determination apparatus characterized by including. The equivalent scattering coefficient of the light propagation path of the light received by the first light receiving means or the second light receiving means is μ _s ′ (t), the speed of light in the scatterer is c, and the short-time pulse light is applied to the observation target. Is a distance from the irradiation position where the first light receiving means receives the light backscattered by the observation target to ρ ₁ , and the light from the irradiation position back scattered by the observation target from the second light receiving means Ρ ₂ , the light intensity acquired by the first light intensity acquisition unit at time t is R (ρ ₁ , t), and the light intensity acquired by the second light intensity acquisition unit at time t. Is R (ρ ₂ , t),
The first equivalent scattering coefficient calculating means calculates an equivalent scattering coefficient of a propagation optical path of light received by the first light receiving means or the second light receiving means from the following equation (1):
The concentration determination apparatus according to claim 1, wherein:

Based on the optical path length of each of the layers of the plurality of light scattering media acquired by the optical path length acquisition unit and the light intensity model acquired by the light intensity model acquisition unit, the equivalent scattering of the arbitrary layer A second equivalent scattering coefficient calculating means for calculating a coefficient;
The light absorption coefficient calculating means includes the light intensity obtained by the first light intensity obtaining means, the second light intensity obtaining means, or the third light intensity obtaining means, and the plurality of light path length obtaining means obtained by the plurality of light intensity acquisition means. The optical path length of each layer of the light scattering medium, the light intensity model acquired by the light intensity model acquisition means, and the equivalent scattering coefficient of the arbitrary layer calculated by the second equivalent scattering coefficient calculation means The concentration determination apparatus according to claim 1, wherein the light absorption coefficient of the arbitrary layer is calculated based on the concentration determination apparatus. The observation object consists of a laminated structure of n layers or more,
The equivalent scattering coefficient of the propagation path of the light received by the first light receiving means or the second light receiving means is μ _s ′ (t), the equivalent scattering coefficient of the m th layer is μ _sm ′, and the average of the m th layer at time t. The optical path length is L _m ′ (t), the optical path length of the m-th layer at time t is L _m (t), and the light intensity at time t of the time-resolved waveform model of the short-time pulsed light is N (t). sometimes,
The first light intensity acquisition unit, the second light intensity acquisition unit, or the third light intensity acquisition unit acquires a light intensity at least for a predetermined time τ1 to τ2,
The second equivalent scattering coefficient calculating means calculates an approximate solution of an equivalent scattering coefficient of each of the plurality of light scattering medium layers from the following equation (2), and is generated from the approximate solution of the equivalent scattering coefficient. Further, a correction value of the optical path length of each of the layers of the light scattering medium at the predetermined time of the model of the propagation optical path length distribution and the predetermined time of the model of the time-resolved waveform of the short-time pulsed light Each of the plurality of layers of the light scattering medium by substituting the correction value of the light path length and the correction value of the light intensity model into the following equation (2): The calculation of the correction value of the equivalent scattering coefficient of each layer of the plurality of light scattering media is repeated until it converges to the true value of the equivalent scattering coefficient of each of the layers of the plurality of light scattering media. To calculate,
The concentration determination apparatus according to claim 3.

The observation object consists of a laminated structure of n layers or more,
The light intensity at time t of the time-resolved waveform model of the short-time pulse light is N (t), and the first light intensity acquisition unit, the second light intensity acquisition unit, or the third light intensity acquisition unit performs the time t R (t), the light absorption coefficient of the m-th layer is μ _am , the optical path length of the m-th layer at time t in the model of the propagation optical path length distribution is L _m (t), and the number of incident photons is N _in , where the incident light intensity is I _in
The first light intensity acquisition unit, the second light intensity acquisition unit, or the third light intensity acquisition unit acquires light intensities at a plurality of times t _{1 to} t _m ,
The light absorption coefficient calculating means calculates the light absorption coefficient of the arbitrary layer from the following equation (3):
The concentration quantification apparatus according to any one of claims 1 to 4, wherein

The observation object consists of a laminated structure of n layers or more,
The light intensity at time t of the time-resolved waveform model of the short-time pulse light is N (t), and the first light intensity acquisition unit, the second light intensity acquisition unit, or the third light intensity acquisition unit performs the time t R (t), the light absorption coefficient of the m-th layer is μ _am , the optical path length of the m-th layer at time t in the model of the propagation optical path length distribution is L _m (t), and the number of incident photons is N _in , where the incident light intensity is I _in
The first light intensity acquisition unit, the second light intensity acquisition unit, or the third light intensity acquisition unit acquires a light intensity between a predetermined time and at least a predetermined time τ1 to τ2,
The light absorption coefficient calculating means calculates the light absorption coefficient of the arbitrary layer from the following equation (4):
The concentration quantification apparatus according to any one of claims 1 to 4, wherein

The observation object consists of a laminated structure of n layers or more,
The light absorption coefficient in the m-th layer which is the arbitrary layer is μ _am , the light absorption coefficient of the i-th component forming the observation target is μ _ai , and the volume concentration of the i-th component forming the observation target is c _vi . When
The concentration calculation means calculates the concentration of the target component in the arbitrary layer from the following equation (5):
The concentration quantification apparatus according to any one of claims 1 to 6, wherein

The observation object consists of a laminated structure of n layers or more,
The light absorption coefficient in the m-th layer, which is the arbitrary layer, is μ _am , the molar extinction coefficient of the i-th component forming the observation target is ε _i , and the molar concentration of the i-th component forming the observation target is c _i . When
The concentration calculation means calculates the concentration of the target component in the arbitrary layer from the following equation (6):
The concentration quantification apparatus according to any one of claims 1 to 6, wherein

  Based on the light absorption coefficient in the arbitrary layer, the concentration calculation means creates a calibration curve from a value obtained by measuring a characteristic whose characteristics are known using multivariate analysis, and obtains a measurement value of an unknown measurement target. The concentration quantification apparatus according to claim 1, wherein the concentration of the target component in the arbitrary layer is calculated by collating with a calibration curve.   10. The glucose concentration contained in the dermis layer is quantified when the observation target is skin and the arbitrary layer is a dermis layer. Concentration determination device. A light absorption coefficient calculation method for calculating a light absorption coefficient in an arbitrary layer among observation targets formed from a plurality of light scattering medium layers,
Intensity of the light back-scattered by the observation target at the predetermined time after the time when the irradiation means irradiates the short-time pulse light, the propagation optical path of the light received by the first light-receiving means or the second light-receiving means Based on the equivalent scattering coefficient, a model of the propagation optical path length distribution in each layer of the plurality of light scattering medium layers generated based on the equivalent scattering coefficient at an arbitrary time, and the equivalent scattering coefficient at an arbitrary time A model of the time-resolved waveform of the generated short-time pulsed light, an optical path length of each of the layers of the plurality of light scattering media at the predetermined time of the model of the propagation optical path length distribution, A first step of obtaining a light intensity at the predetermined time of the model of the time-resolved waveform;
A second step of calculating a light absorption coefficient of the arbitrary layer based on the light intensity acquired in the first step, the optical path length of each of the layers of the plurality of light scattering media, and the light intensity model . When,
The light absorption coefficient calculation method characterized by having. The equivalent scattering coefficient of the propagation path of the light received by the first light receiving means or the second light receiving means is μ _s ′ (t), the speed of light in the scatterer is c, and the observation target is irradiated with the short-time pulsed light. Ρ ₁ , the distance from the irradiated position to the position where the first light receiving means receives the light backscattered by the observation target, and the light received by the second light receiving means backscattered by the observation target from the irradiation position When the distance to the position is ρ ₂ , the light intensity acquired at time t is R (ρ ₁ , t) , and the light intensity acquired at time t is R (ρ ₂ , t),
In the first step, an equivalent scattering coefficient of a propagation optical path of light received by the first light receiving means or the second light receiving means is calculated from the following equation (1):
The light absorption coefficient calculation method according to claim 11.

In the first step, an equivalent scattering coefficient of the arbitrary layer is obtained based on the optical path length of each of the layers of the plurality of light scattering media, the light intensity model,
In the second step, the light intensity acquired in the first step, the optical path length of each of the layers of the plurality of light scattering media, the light intensity model, and the equivalent scattering coefficient of the arbitrary layer 13. The light absorption coefficient calculation method according to claim 11, wherein the light absorption coefficient of the arbitrary layer is calculated based on the calculation result. The observation object consists of a laminated structure of n layers or more,
The equivalent scattering coefficient of the propagation path of the light received by the first light receiving means or the second light receiving means is μ _s ′ (t), the equivalent scattering coefficient of the m th layer is μ _sm ′, and the average of the m th layer at time t. The optical path length is L _m ′ (t), the optical path length of the m-th layer at time t is L _m (t), and the light intensity at time t of the time-resolved waveform model of the short-time pulsed light is N (t). sometimes,
In the first step, obtaining a light intensity at least for a predetermined time τ1 to τ2,
The approximate solution of the equivalent scattering coefficient of each of the layers of the plurality of light scattering media is calculated from the following equation (2), and the model of the propagation optical path length distribution generated from the approximate solution of the equivalent scattering coefficient is calculated. A correction value of the optical path length of each of the layers of the plurality of light scattering media at a predetermined time, and a correction value of the light intensity at the predetermined time of the time-resolved waveform model of the short-time pulsed light. Obtaining and substituting the correction value of the optical path length and the correction value of the light intensity model into the following equation (2), the correction value of the equivalent scattering coefficient of each layer of the plurality of light scattering media is obtained. Calculating the equivalent scattering coefficient of the arbitrary layer by repeatedly calculating until it converges to the true value of the equivalent scattering coefficient of each layer of the plurality of light scattering media,
The light absorption coefficient calculation method according to claim 13.

The observation object consists of a laminated structure of n layers or more,
The equivalent scattering coefficient of the propagation light path of the light received by the first light receiving means or the second light receiving means is μ _s ′ (t), the equivalent scattering coefficient of the m th layer is μ _sm ′, and the average optical path length of the m th layer at time t. Is L _m ′ (t), the optical path length of the m-th layer at time t is L _m (t), and the light intensity at time t of the time-resolved waveform model of short-time pulsed light is N (t),
Obtaining the light intensity at least for a predetermined time τ1 to τ2,
An approximate solution of the equivalent scattering coefficient of each of the layers of the light scattering medium is calculated from the following equation (2), and the time of the model of the propagation optical path length distribution generated from the approximate solution of the equivalent scattering coefficient is calculated. a correction value of the optical path length of each of the layers of the light scattering medium at t and a correction value of the light intensity at the predetermined time of the model of the time-resolved waveform of the short-time pulse light. Then, by substituting the correction value of the optical path length and the correction value of the light intensity model into the following equation (2), the correction value of the equivalent scattering coefficient of each of the layers of the plurality of light scattering media is calculated. The equivalent scattering coefficient calculation method is characterized in that the equivalent scattering coefficient of the arbitrary layer is calculated by repeatedly performing until the true value of the equivalent scattering coefficient of each layer of the plurality of light scattering media converges. .

A concentration quantification method, wherein the concentration of a target component in the arbitrary layer is calculated based on the light absorption coefficient calculated in the second step according to any one of claims 11 to 14.   The concentration quantification method according to claim 16, wherein when the observation target is skin and the arbitrary layer is a dermis layer, the concentration of glucose contained in the dermis layer is quantified. Computer, irradiating means for irradiating a short pulsed light observation object formed from multiple layers of light scattering medium,
A first receiving means for receiving light the short pulsed light is backscattered by the observed object,
The distance from the irradiation position at which the short-time pulsed light is back-scattered by the observation target and the position at which the short-time pulsed light is irradiated to the observation target to the position at which the back-scattered light is received by the observation target a second light receiving means but arranged to be different from the first light receiving means,
A first light intensity acquisition means for acquiring the intensity of the light the first light receiving means has received the predetermined time after the time of the irradiation unit irradiates the short pulse light,
A second light intensity acquisition means for acquiring the intensity of the second light received by the light receiving section at a predetermined time after the time of the irradiation unit irradiates the short pulse light,
Based on the light intensity acquired by the first light intensity acquisition means and the light intensity acquired by the second light intensity acquisition means, the equivalent of the propagation optical path of the light received by the first light receiving means or the second light receiving means a first scattering coefficient calculation means for calculating a scattering coefficient,
An optical path length distribution storing a propagation optical path length distribution model in each of the layers of the plurality of light scattering media generated based on the equivalent scattering coefficient at an arbitrary time calculated by the first equivalent scattering coefficient calculating means. a storage means,
Wherein the first scattering coefficient calculation means is generated based on the scattering coefficient at any time calculated, the time-resolved waveform storage means for storing a model of the time-resolved waveform of the short pulse light,
From the optical path length distribution storage means, in the predetermined time in the model of the propagation optical path length distribution, the optical path length acquisition means for acquiring an optical path length of each layer of the layer of the plurality of light scattering medium,
From the time-resolved waveform storage means, and the light intensity model acquiring means for acquiring the intensity of the light in the predetermined time in the model of the time-resolved waveform of the short pulse light,
The light intensity acquired by the first light intensity acquisition means, the second light intensity acquisition means, or a third light intensity acquisition means different from the first light intensity acquisition and the second light intensity acquisition means, and the optical path length A light absorption coefficient of an arbitrary layer is calculated based on the optical path length of each layer of the plurality of light scattering media acquired by the acquisition unit and the light intensity model acquired by the light intensity model acquisition unit. a light absorption coefficient calculating means,
A program that calculates the light absorption coefficient to function as The equivalent scattering coefficient of the light propagation path of the light received by the first light receiving means or the second light receiving means is μ _s ′ (t), the speed of light in the scatterer is c, and the short-time pulse light is applied to the observation target. Is a distance from the irradiation position where the first light receiving means receives the light backscattered by the observation target to ρ ₁ , and the light from the irradiation position back scattered by the observation target from the second light receiving means Ρ ₂ , the light intensity acquired by the first light intensity acquisition unit at time t is R (ρ ₁ , t), and the light intensity acquired by the second light intensity acquisition unit at time t. Is R (ρ ₂ , t),
The first equivalent scattering coefficient calculating means calculates an equivalent scattering coefficient of a propagation optical path of light received by the first light receiving means or the second light receiving means from the following equation (1):
The program for calculating the light absorption coefficient according to claim 18.

Based on the optical path length of each of the layers of the plurality of light scattering media acquired by the optical path length acquisition means and the light intensity model acquired by the light intensity model acquisition means, Second equivalent scattering coefficient calculating means for calculating the equivalent scattering coefficient of
Function as
The light absorption coefficient calculating means includes the light intensity obtained by the first light intensity obtaining means, the second light intensity obtaining means, or the third light intensity obtaining means, and the plurality of light path length obtaining means obtained by the plurality of light intensity acquisition means. The optical path length of each layer of the light scattering medium, the light intensity model acquired by the light intensity model acquisition means, and the equivalent scattering coefficient of the arbitrary layer calculated by the second equivalent scattering coefficient calculation means 20. The program for calculating a light absorption coefficient according to claim 18, wherein the light absorption coefficient of the arbitrary layer is calculated based on the program. The observation object consists of a laminated structure of n layers or more,
The equivalent scattering coefficient of the propagation path of the light received by the first light receiving means or the second light receiving means is μ _s ′ (t), the equivalent scattering coefficient of the m th layer is μ _sm ′, and the average of the m th layer at time t. The optical path length is L _m ′ (t), the optical path length of the m-th layer at time t is L _m (t), and the light intensity at time t of the time-resolved waveform model of the short-time pulsed light is N (t). sometimes,
The first light intensity acquisition unit, the second light intensity acquisition unit, or the third light intensity acquisition unit acquires a light intensity at least for a predetermined time τ1 to τ2,
The second equivalent scattering coefficient calculating means calculates an approximate solution of an equivalent scattering coefficient of each of the plurality of light scattering medium layers from the following equation (2), and is generated from the approximate solution of the equivalent scattering coefficient. Further, a correction value of the optical path length of each of the layers of the light scattering medium at the predetermined time of the model of the propagation optical path length distribution and the predetermined time of the model of the time-resolved waveform of the short-time pulsed light Each of the plurality of layers of the light scattering medium by substituting the correction value of the light path length and the correction value of the light intensity model into the following equation (2): The calculation of the correction value of the equivalent scattering coefficient of each layer of the plurality of light scattering media is repeated until it converges to the true value of the equivalent scattering coefficient of each of the layers of the plurality of light scattering media. To calculate,
The program for calculating the light absorption coefficient according to claim 20 .

A computer is caused to function as a concentration calculation unit that calculates a concentration of a target component in the arbitrary layer based on the light absorption coefficient calculated by the light absorption coefficient calculation unit according to any one of claims 18 to 21. Program to calculate the concentration of the   23. The program for calculating a concentration according to claim 22, wherein when the observation target is skin and the arbitrary layer is a dermis layer, the concentration of glucose contained in the dermis layer is quantified.

Images