JP6521307B2 - Method and apparatus for measuring biological property values using near infrared spectroscopy - Google Patents

Description

  The present invention relates to a method and apparatus for measuring biological property values such as blood glucose levels using near infrared spectroscopy.

  The measurement of biological property values generally involves blood collection. For example, as a method of measuring blood glucose level in a human, the reaction of glucose oxidase to blood glucose is electrochemically quantified using blood collected, and blood glucose is measured A glucose sensor method has been established to convert to a value.

  On the other hand, in order to solve problems such as pain associated with blood collection and infection with a blood collection needle, methods of non-invasively measuring biological property values have been proposed, and one of them is near infrared spectroscopy. The measuring method used is known. This is to irradiate the light of the wavelength of near infrared region to a specific part of the living body (human body), measure the diffuse reflection light or the transmitted light from the living body with a spectroscope, and absorb the absorbance of the diffuse reflected light or the transmitted light ( It is intended to calculate biological characteristic values such as blood sugar level from the spectrum).

  In the measurement of blood glucose level, a method is known in which light of a wavelength in the near infrared region including a specific wavelength of 920 nm and a specific wavelength of 982 nm is irradiated to a finger or the like to obtain its absorbance and measure the blood glucose level from that value. ing. Moreover, in the thing of following patent document 1, measuring non-invasively the blood glucose level of a human body from the transmitted light amount from the human body obtained by irradiating the light which consists of several different wavelengths to a human body is proposed. .

Patent No. 4052461 gazette

  In the measurement of biological property values, it is important to measure how the biological property values change with the passage of time in accordance with the state of the living body to be measured. For example, in the case of measurement of blood glucose level, if changes in blood glucose levels after meals are known, food ingredients that can suppress the rise in blood glucose levels after meals are found, and health management such as prevention of obesity or diabetes is prevented. It can be useful.

  When measuring changes in biological property values with the passage of time, it is necessary to collect blood every fixed time (for example, every several tens of minutes) when trying to measure using collected blood, a large burden on the subject of measurement There is a problem that you If the noninvasive measurement method is established like the prior art mentioned above, this problem will be solved, but if it is going to obtain the change over time of the biological property value by near infrared spectroscopy, the biological property value will be It becomes difficult to select a specific wavelength for obtaining the related absorbance, and there arises a problem that an accurate value can not be determined.

  When biological property values such as blood glucose levels are determined by near infrared spectroscopy, the absorbance related to the biological property values is determined according to the state to be measured for each individual to be measured or even the same individual and the difference between the days. It has been found that the particular wavelengths obtained are different. For this reason, as in the prior art, even when trying to determine the absorbance with a specific wavelength as a fixed value and determine the correlation between the absorbance and the biological characteristic value, individual differences and differences between days, body temperature changes at the measurement site, sweating conditions, etc. There is a problem that an accurate value can not be obtained due to a state difference, an optical path change in a living tissue at a measurement site, or the like, and a large difference with an actual measurement value occurs.

  The present invention takes an example of the problem to address such a problem. That is, a method of measuring a new biological property value using near-infrared spectroscopy is proposed, and measurement of the biological property value with high accuracy is enabled, and a change of the biological property value with the passage of time to the person to be measured. It is an object of the present invention to be able to measure with high accuracy while reducing the burden.

  In order to achieve such an object, the method and apparatus for measuring biological characteristic values using near-infrared spectroscopy according to the present invention have the following configurations.

A near-infrared spectroscopy biological characteristic value measuring method using the measuring changes with time of the biological characteristic values, in a plurality of elapsed time, is irradiated with near-infrared light to the raw body, diffusion from a living body Reflected light or transmitted light is received to determine the absorbance for each of a plurality of wavelengths in the near-infrared set wavelength range, and a wavelength having a high correlation of absorbance with the measured value of the biological measurement value obtained in the plurality of elapsed times To calculate the measured value from the absorbance of the specified wavelength, and at other elapsed times, irradiate the living body with near infrared light and receive diffuse reflected light or transmitted light from the living body It is characterized in that the absorbance of the specified wavelength is determined, and the biological characteristic value is calculated from the calculation formula.

  In a biological property value measuring apparatus using near infrared spectroscopy that measures changes with time of biological property values, arithmetic processing is performed on the measured values of the input biological property values and the absorbance obtained by the near infrared spectroscope. When the arithmetic processing unit measures changes in the biological characteristic value with the passage of time, the measured values of the biological characteristic value measured in a plurality of elapsed times and the set wavelength of the near infrared light From the absorbance determined for each of a plurality of wavelengths in the range, a wavelength having a high correlation of absorbance with the measured value is identified, and a calculation formula for calculating the measured value from the absorbance of the identified wavelength is derived. A biological property value measuring apparatus using near-infrared spectroscopy, which calculates a biological property value from the absorbance of a specified wavelength and the formula in time.

  In the present invention having such characteristics, when measuring the change over time of the biological characteristic value, the optimum wavelength is specified for each series of measurement to obtain the absorbance, and the biological characteristic value is determined by the correlation with the absorbance. As it can be determined, it is possible to measure biological characteristic values with high accuracy by near infrared spectroscopy. In addition, since the change of the biological characteristic value with the passage of time can be measured without obtaining a part of the actual measurement value, it is possible to accurately measure while reducing the burden on the person to be measured associated with blood collection and the like.

  Furthermore, according to the present invention, the optimum wavelength is specified for each measurement even if there are individual differences, daily differences, temperature changes in the measurement site, state differences such as sweating conditions, or changes in the optical path in living tissues at the measurement site. Then, the biological characteristic value can be calculated by obtaining the absorbance having a high correlation with the biological characteristic value, whereby a living body capable of securing stable measurement accuracy applicable to anyone anytime, anywhere, and anyone A characteristic value measuring method and apparatus can be provided.

It is an explanatory view showing an example of composition of a living body characteristic value measuring device concerning an embodiment of the present invention. It is explanatory drawing which showed the measurement result of the biological property value calculated | required by the arithmetic processing part. It is explanatory drawing which showed the data input into an arithmetic processing part.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings. FIG. 1 is an explanatory view showing a configuration example of a biological characteristic value measuring device according to an embodiment of the present invention. The biological characteristic value measuring device 1 includes a near infrared spectroscopy device 10 and an arithmetic processing unit 20. The near-infrared spectrometer 10 has a known configuration, and includes a photometric unit 11, a spectral unit 12, and a light source unit 13. The photometry unit 11 receives the diffusely reflected light or the transmitted light from the object to be measured (living body) M, and the light emitting unit 14 that irradiates the object to be measured (living body) M with near infrared light emitted from the light source unit 13 The light receiving unit 15 is provided. The spectroscope unit 12 obtains the absorbance of a specific wavelength from the light received by the light receiver 15 and outputs the absorbance. The arithmetic processing unit 20 receives an actual measurement value of the biological property value and receives a measured value of the absorbance output from the spectroscopic unit 12 and performs arithmetic processing on them to obtain the biological characteristic of the elapsed time not measured. Calculate and output the value.

  The biological characteristic value measuring method using near infrared spectroscopy according to the embodiment of the present invention is executed by the processing process of the arithmetic processing unit 20. The processing steps of the arithmetic processing unit 20 will be described below.

FIG. 2 shows the measurement results of the biological property values obtained by the arithmetic processing unit 20. Here, the change with time progress of the biological property value is calculated, and a part is obtained by actual measurement to calculate how to change the biological property value at the elapsed time t0 to t6 from the start of measurement, and others are calculated. It is calculated by the value. Here, the actual measurement value refers to a value measured from blood obtained by blood collection. The blood for which the measured value has been obtained is discarded without being returned to the human body.

Specifically, an actual measurement value A0 of the biological property value at the elapsed time t0, an actual measurement value A1 of the biological property value at the elapsed time t1, an actual measurement value A2 of the biological property value at the elapsed time t2, and an actual measurement of the biological property value at the elapsed time t3. The measured values A3 of the biological property values at the elapsed time t6 are obtained respectively, and the biological property values at the elapsed time t4 are obtained from the absorbances obtained by the near-infrared spectrometer at each elapsed time t0 to t6 and the measured values described above Calculated value) A4 ^* , and a biological property value (calculated value) A5 ^* at elapsed time t5 are calculated.

The arithmetic processing unit 20, as shown in FIG. 3, the measured values A0, A1, A2, A3, A6, absorbance I _.lambda.i ^t is input. Absorbance I _.lambda.i ^t is the elapsed time t (= t1, t2, ... , t6) Wavelength .lambda.i in (= λ1, λ2, ..., λn-1, λn) is absorbance. The wavelength λi is a plurality of wavelengths determined by the set wavelength range of near-infrared light, for example, a wavelength set every few to several tens of nm in the range of 700 to 1050 nm, and λ1 = 700 nm, λ2 It can be set every 1 nm, such as = 701 nm, λ 3 = 702 nm, ..., λ n -1 = 1049 nm, λ n = 1050 nm.

The arithmetic processing unit 20 obtains a correlation coefficient of (absorbance, actual measurement value) for each wavelength λi. That is, for each wavelength .lambda.i, correlation coefficient ^{_{(I λi t0, A0),}} (I λi t1, A1), (I λi t2, A2), (I λi t3, A3), (I λi t6, A6) Ask for Then, one or more wavelengths λi having high correlation coefficients are identified. Here, that the correlation coefficient is high can be set to an absolute value of the correlation coefficient of 0.7 or more, or an absolute value (maximum value) of the highest correlation coefficient-0.1 or more.

Assuming that a wavelength having a high correlation coefficient is λt, a formula for calculating an actual measurement value from the absorbance I _λt ^t of the wavelength λt is derived. When multiple wavelengths λt are specified, the value (weighted sum) obtained by multiplying the absorbance of each specified wavelength by the correlation of the wavelengths and adding them together is the explanatory variable (X), and the biological property value is the target variable ( As Y), simple regression is performed to estimate the value of the coefficient a and the intercept b for which Y = a · X + b holds, and the formula is used to convert the absorbance into a biological property value by this Y = a · X + b.

Then, I _λt ^t4 and I _λt ^t5 are substituted for the explanatory variable X, and biological characteristic values A4 ^* and A5 ^* at elapsed times t4 and t5 are calculated from Y = a · X + b. According to such a method of measuring a biological characteristic value, when measuring a change in the biological characteristic value with elapsed time, acquisition of an actual measurement value accompanied by blood collection can be stopped at a part of the elapsed time, and other elapsed time Since the measurement in the above can be compensated by a calculated value not accompanied by blood collection etc., highly accurate measurement can be realized while reducing the burden on the person to be measured.

  In the above description, the example of obtaining the biological property value from the absorbance is shown, but instead of that, the amount of change in the biological property value may be obtained from the amount of change in absorbance. When obtaining the biological property value from the absorbance or when obtaining the biological property value from the amount of change in the absorbance, the sum of the absorbance due to the difference in the light diffusion state with respect to the absorbance for each wavelength obtained in one measurement In order to remove the multiplicative fluctuation, it is preferable to perform the second derivative processing in advance by the Savitzky-Golay method. In addition to the second derivative processing, methods such as SC (Multiplicative Scatter Correction) and SNV (Standard Normal Variate) can also be adopted.

  Hereinafter, an example of taking a blood glucose level of a person as an example of the biological characteristic value and measuring GI of a food based on a change in blood glucose level along with a time course after eating will be described.

  GI (glycemix index) is an index showing the degree of increase in postprandial blood glucose levels, and by searching for GI for each food and specifying a low GI food, eating habits from the viewpoint of prevention and improvement of obesity and diabetes It is considered to be an effective indicator for reviewing. GI is defined as GI = (IAUC of test food / IAUC of reference food) × 100, and is determined by an oral glucose tolerance test by a large number of subjects. Here, IAUC refers to the area under the blood sugar level rising curve up to 2 hours after a meal, and it is possible to obtain the blood sugar level change (blood sugar level change amount) with time lapse from 2 hours after a meal to 2 hours It is essential.

In order to obtain one IAUC of the test food or the reference food, the blood glucose level change amount ΔBGt from before eating (fasting) in one subject, elapsed time t = 0 (fasting), 15, 30, 45, Seven measurements of 60, 90, and 120 min are required. For that purpose, measurement is performed using the above-described biological characteristic value measuring apparatus 1, and after the subject eats the test food or the reference food, the elapsed time t = 0 (fasting), 15, 30, 45, 60, 90, 120 min. At each wavelength λ, the amount of change in absorbance from fasting (second derivative value) ΔI _λ is determined. However, it is assumed that λ = 700, 701, ... 851, 852, ..., 1050 nm. At the same time, blood is collected from the subject except for elapsed times of 60 min and 90 min, and measured blood glucose levels at elapsed times t = 0 (fasting), 15, 30, 45, and 120 min. The measured blood glucose level is measured by the glucose sensor method on the blood collected at each elapsed time.

As a result, the arithmetic processing unit 20 calculates the blood glucose level change amount ΔBGt of the measured value measured every elapsed time t = 0, 15, 30, 45, 120 min and the elapsed time t = 0, 15, 30, 45, 60. , amount of change in absorbance was measured every _90,120min ΔI λ is input. The arithmetic processing unit 20 _determines the correlation coefficient r of the blood sugar value change amount ΔBGt and the absorbance change amount ΔI _λ for each wavelength λ based on the input data, and specifies the wavelength λ ^* having a high correlation. Here, since the second derivative value is applied as the absorbance change amount, the correlation coefficient r between the blood glucose level change amount ΔBGt and the absorbance change amount ΔI _λ becomes a negative value. Of a high wavelength lambda ^* correlation, corresponding wavelength lambda ^* a to s specified below negative maximum value +0.1 of the correlation coefficient r.

The arithmetic processing unit 20 measures the amount of change in absorbance ΔI _{λ *} ^t (t = 0, 15, 30, 45, 120 min) at the specified wavelength λ ^* and the amount of change in blood glucose value ΔBGt (t = 0, 15, 30, From 45, 120 min), a calculation formula is derived in which the blood glucose level change amount ΔBGt is the target variable (Y) and the absorbance change amount ΔI _{λ *} is the explanatory variable (X). Specifically, single regression analysis of the objective variable (Y) and the explanatory variable (X) is performed to obtain a and b of Y = a + b · X. Here, when a plurality of wavelengths λ ^* are specified, the explanatory variable (X) is a weighted sum of absorbance change amounts ΔI _{λ *} (Σr ^* · ΔI _{λ *} , r ^* is a correlation coefficient for each λ ^* ) Do.

Using this formula (Y = a + b · X), X = ΔI _{λ *} (t = 60 min) is substituted to obtain Y = ΔBGt (t = 60 min), and X = ΔI _{λ *} (t = 90 min) To obtain Y = .DELTA.BGt (t = 90 min). Thereby, the blood glucose level change amount ΔBGt, which is a part of the actual measurement value and a part of the calculation value, is calculated seven times, with an elapsed time t = 0 (fasting), 15, 30, 45, 60, 90, 120 min. It is possible to measure, and from this measurement result, it is possible to determine the IAUC of the test food or the reference food.

  As described above, according to the measuring method and measuring apparatus according to the embodiment of the present invention, when measuring the change over time of the biological property value, the optimum wavelength is specified to determine the absorbance for each series of measurement. Since the biological characteristic value can be determined by the correlation with the absorbance, it is possible to measure the biological characteristic value with high accuracy by near infrared spectroscopy. In addition, since changes in the biological characteristic value with the passage of time can be measured without obtaining a part of the actual measurement value, it is possible to accurately measure the biological characteristic value while reducing the burden on the person to be measured accompanying blood collection and the like. Can.

  In particular, GI (glycemix index) measurement, which is attracting attention for prevention and improvement of diabetes and obesity in the food field, and blood sugar level control of diabetes patients in the medical field, is an examination to find out GI of food. It is necessary for the subject to actually ingest the food and reference food and to carry out an oral glucose tolerance test to measure changes in blood glucose level after intake, in which case conventionally one IAUC (increase in blood glucose level up to 2 hours after a meal) In order to obtain the area under the curve, 7 blood samples were required within 2 hours, but when using the measurement method of the present invention, some of the blood samples were omitted and the actual values were replaced with calculated values. In addition, it is possible to obtain a highly accurate IAUC. This makes it possible to reduce the burden on the subject in GI measurement.

1: Biological characteristic value measuring device, 10: Near infrared spectroscopy device, 11: Photometric unit,
12: Spectroscopic part, 13: Light source part, 14: Light irradiation part, 15: Light receiving part,
20: Arithmetic processing unit, M: object to be measured

Claims (5)

A method of measuring a biological property value using near infrared spectroscopy, which measures a change in biological property value with time .
A plurality of elapsed time, is irradiated with near-infrared light to the raw body, by receiving diffuse reflected light or transmitted light from the living body, seeking the absorbance of each of a plurality of wavelengths in a predetermined wavelength range of the near-infrared, the plurality Identifying a wavelength at which the correlation of the absorbance is high with respect to the measured value of the biological measurement value in the elapsed time of, and deriving a calculation formula for calculating the measured value from the absorbance of the specified wavelength,
In the other elapsed time, the living body is irradiated with the near infrared light, the diffuse reflection light or the transmitted light from the living body is received, the absorbance of the specified wavelength is determined, and the biological property value is calculated from the calculation formula. A method for measuring biological property values using near-infrared spectroscopy characterized by   The biological characteristic value measuring method using near infrared spectroscopy according to claim 1, wherein the absorbance for each of the plurality of wavelengths is determined every several to several tens of nm in a wavelength range of 700 to 1050 nm. .   The method for measuring a biological characteristic value using near infrared spectroscopy according to claim 1 or 2, wherein the absorbance is a second derivative value with respect to an elapsed time. The near-infrared spectroscopy according to any one of claims 1 to 3, wherein the biological characteristic value is a blood glucose level, and the actual measurement value is a value obtained by a glucose sensor method using blood collection. Method of measuring biological characteristics using the method. In a biological characteristic value measuring apparatus using near infrared spectroscopy which measures a change over time of the biological characteristic value,
It has an arithmetic processing unit that performs arithmetic processing on the measured values of the input biological property values and the absorbance determined by the near infrared spectrometer.
The arithmetic processing unit
When measuring the change over time of the biological characteristic value,
Identify the wavelength with high correlation of absorbance with the actual measurement value from the actual measurement value of the measured biological property value and the absorbance calculated for each of multiple wavelengths in the near-infrared setting wavelength range in multiple elapsed times Derive a formula for calculating the actual measurement value from the absorbance of the specified wavelength,
A biological characteristic value measuring apparatus using near infrared spectroscopy, wherein a biological characteristic value is calculated from the absorbance of the specified wavelength and the formula at other elapsed times.

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