JP2007097654A - Blood information measuring device - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To non-invasively measure blood sugar information using photoacoustic spectroscopy. <P>SOLUTION: By a blood information measuring device 10, a tomographic image of a biological tissue can be acquired by optical interference tomography, and the position of the blood vessel is specified from the acquired tomographic image. A rod lens 28 can be moved in the optical axis direction, and can move the focal position of measuring light. After the position and depth of the blood vessel are specified, the focal position of the measuring light is positioned inside the blood vessel to make the measuring light irradiate a subject. Pressure wave emitted from inside of the subject is detected as ultrasonic wave, and the amount of glycohemoglobin can be measured by the intensity of the ultrasonic wave. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a blood information measuring device for measuring blood glucose information such as glycohemoglobin.

  HbA1c, which is a kind of glycohemoglobin in which hemoglobin and glucose are combined in blood, is an indicator of the average blood glucose level over the past 1 to 3 months. Used for occasions. Conventionally, blood is collected from a subject and quantitatively measured for HbA1c by a reagent reaction or a chromatography method. In recent years, it has been proposed to use photo-acoustic spectroscopy (PAS) as a non-invasive measurement method that does not involve blood collection (Non-Patent Document 1).

In photoacoustic spectroscopy, for example, when a specific tissue or substance that becomes a light absorber is irradiated with measurement light of the maximum absorption wavelength for a short time, light energy is converted into heat by the light absorber, and the light absorber The pressure wave generated by instantaneous expansion is used. When this pressure wave is transmitted through the air as an ultrasonic wave and is detected by a high-performance microphone, a strong PAS signal is obtained from a portion where the light absorber is contained in a large proportion.
Nao Wadamori and Junichi Matsuda Basic study on HbA1c concentration monitoring by photoacoustic spectroscopy Biomedical Engineering 2004 42-3 159/166

  However, as described in Non-Patent Document 1, when PAS is used for living tissue, since the PAS signal is weak, the SN ratio with the background noise is poor, and the measurement accuracy is low. is there. Further, since HbA1c exists only in blood vessels, when a PAS signal is obtained from a wide range, the signal intensity is averaged, and the SN ratio is further deteriorated.

  The present invention has been made in consideration of the above problems, and an object of the present invention is to provide a blood glucose information measuring device capable of improving the accuracy for measuring HbA1c using PAS.

  To achieve the above object, the blood information measuring device of the present invention includes a blood vessel specifying means for specifying the position of a blood vessel, a measurement light collecting means for collecting measurement light at the specified blood vessel position, and the measurement. Photoacoustic signal detection means for detecting a sound wave generated by an absorber in blood that has absorbed light as a photoacoustic signal, and blood glucose information measurement means for measuring blood glucose information in the blood based on the photoacoustic signal It is characterized by.

  In addition, a tomographic signal generating unit that generates a tomographic signal indicating the tomographic information of the biological tissue is provided, and the blood vessel specifying unit specifies a position of the blood vessel based on the tomographic information.

  As the blood glucose information, at least one of glycated protein and glucose is measured.

  The measurement light includes two types of light having different wavelengths in order to generate two-photon absorption.

  According to the present invention, since the photoacoustic signal can be obtained by the measurement light focused on the blood vessel by specifying the blood vessel position, the output level of the photoacoustic signal is increased and the SN ratio can be increased. As a result, a non-invasive blood glucose information measuring device with improved accuracy for measuring glycated protein can be obtained.

  Further, since the blood vessel position is identified from the tomographic signal indicating the tomographic information of the living body, the measurement light is accurately collected in consideration of the blood vessel depth that is the depth from the living body surface to the blood vessel, so that the SN ratio is further increased. Measurement accuracy can be improved.

  In addition, by using two-photon absorption, the influence of scattering can be reduced and a strong photoacoustic signal can be obtained. Furthermore, since two-photon absorption occurs only in a high energy density range, detection with a high S / N ratio is possible. Thus, measurement accuracy can be improved.

  In FIG. 1, a blood information measuring apparatus 10 identifies a blood vessel using one of optical interference tomography (OCT) and photoacoustic tomography (PAT), and photoacoustics. Blood glucose information is measured by spectroscopy (PAS: Photo Acoustic Spectroscopy). The blood information measuring apparatus 10 includes an optical unit 11 for irradiating a living tissue with measurement light and an electric circuit unit 12 to which an electric signal is input from each sensor.

  The optical unit 11 includes a light source unit 15 that emits light necessary for measurement, a fiber coupler 16 that divides the light from the light source unit 15 into measurement light and reference light, and recombines the divided measurement light and reference light. The optical path difference adjusting unit 18 provided with the reference mirror 17, the photodetector 19 for detecting the combined light obtained by combining the measuring light and the reference light, and the irradiating unit 20 for irradiating the subject with the measuring light. ing. An optical fiber 21 is connected between the light source unit 15 and the optical path difference adjusting unit 18, and between the photodetector 19 and the irradiation unit 20, and becomes an optical path of light from the light source unit 15. A piezo element 22 is provided between the fiber coupler 16 and the optical path difference adjusting unit 18. The piezo element 22 functions as a frequency shifter that causes a slight frequency shift in the reference light.

  The light source unit 15 is provided with four types of light sources. The light source 15a is composed of a near-infrared SLD (Super Luminescent Diode), and emits high-luminance and low-coherent light for obtaining an OCT image. The light source 15b, the light source 15c, and the light source 15d are light emitting diodes that emit light of 514 nm, 830 nm, and 1600 nm, respectively. The light source 15b and the light source 15c are used when obtaining tomographic information of a living tissue by a photoacoustic tomography method when measuring HbA1c by photoacoustic spectroscopy. Used for light source. The light source 15d is used when measuring blood glucose concentration.

  The optical path difference adjusting unit 18 receives the reference light divided by the fiber coupler 16. A condenser lens 25 is provided immediately before the reference mirror 17. The reference mirror 17 is given a driving force by the driving unit 26 and moves in the horizontal direction in the figure. Thereby, an optical path length difference occurs between the reference light and the measurement light. The photodetector 19 has a condensing lens 27 in front of it.

  The irradiation unit 20 irradiates the subject with measurement light. The irradiation unit 20 includes a rod lens 28 that condenses the light from the fiber coupler 16, a reflection mirror 29 that bends the path of the measurement light by 90 degrees, and an ultrasonic wave that detects ultrasonic waves emitted from the direction in which the measurement light is irradiated. And a detector 30. The irradiation unit 20 can move in a two-dimensional direction within a predetermined plane or a three-dimensional direction including a height direction according to the surface of the subject, and can scan the subject while irradiating measurement light. . The irradiation unit 20 may be fixed and the subject may be placed on a movable stage.

  The electric circuit unit 12 includes a rod lens driving unit 33, an ultrasonic signal processing unit 34, an optical tomographic signal generation unit 35, and a central processing unit 36. The rod lens drive unit 33 is a drive source for moving the rod lens 28 in the optical axis direction, and changes the focal position of the measurement light. The ultrasonic signal processing unit detection unit rod lens driving unit 33 and the ultrasonic signal detected by the ultrasonic detector 30 are amplified and noise is removed. The optical tomographic signal generation unit 35 extracts an interference image between the measurement light and the reference light detected by the photodetector 19 as an optical tomographic signal and sends it to the central processing unit 36.

  The central processing unit 36 functions as a system control unit 39, a tomographic image generation unit 40, a blood vessel discrimination unit 41, a focal position control unit 42, and a measurement unit 43 by executing a program. The system control unit 39 controls the operation of parts that require electric power, such as the photodetector 19 and the rod lens driving unit 33, and causes each unit to function according to a predetermined procedure. The tomographic image generation unit 40 constructs a tomographic image of the subject based on the optical tomographic signal sent from the optical tomographic signal generation unit 35. When a tomographic image is displayed on the tomographic image display monitor 45, an input operation is performed on the region-of-interest setting unit 46 based on the judgment of the measurer, and a specific region of the tomographic image is set as the region of interest R1. The blood vessel discrimination unit 41 detects a blood vessel image from the region of interest of the tomographic image. The measurement unit 43 specifies the position and depth of the detected blood vessel. The focal position control unit 42 calculates a driving amount of the rod lens driving unit 33 necessary for focusing the measurement light on the specified blood vessel position. The calculated driving amount is sent to the rod lens driving unit 33.

  Next, the operation of blood information measuring apparatus 10 will be described. When the blood glucose level measurement is started, the system control unit 39 turns on the light source 15a that is an SLD. The light from the light source 15 a propagates through the optical fiber 21 and is divided into reference light and measurement light by the fiber coupler 16. The reference light is modulated by the piezoelectric element 22, and a slight frequency difference is generated between the reference light and the measurement light. The measurement light is irradiated from the irradiation unit 20 to the subject. Of the measurement light incident on the subject, the measurement light reflected at a predetermined depth of the test part returns to the irradiation unit 20, and the measurement light and the reference light are combined in the fiber coupler 16.

  Since the measurement light and the reference light are low coherent light with a short coherence distance, when the measurement light and the reference light have the same optical path length and there is no difference in the optical path, depending on the magnitude of the frequency difference An optical beat with a certain period occurs. This is detected by the photodetector 19, and an optical tomographic signal having tomographic information is extracted by the optical tomographic signal generator 35. The optical tomographic signal is sent to the tomographic image generation unit 40. When a living subject is scanned linearly, a continuous optical tomographic signal is obtained, and a two-dimensional tomographic image is generated by the tomographic image generation unit 40.

  The generated tomographic image is displayed on the tomographic image display monitor 45. The person in charge of measurement confirms the displayed tomographic image and sets a region considered to be a blood vessel as a region of interest via the region of interest setting unit 46. When the region of interest R is set, the blood vessel discriminating unit 41 identifies the position of the blood vessel existing inside the region of interest R, and obtains the position and depth of the blood vessel by image measurement. The focal position control unit 42 determines the focal position of the rod lens 28 from the obtained blood vessel position and depth. The rod lens driving unit 33 moves the rod lens 28.

  The system control unit 39 turns on the light source 15b and the light source 15c at the same timing, and irradiates the subject with measurement light. The measurement light is most narrowed inside the blood vessel by the rod lens 28, and the intensity of the incident measurement light becomes the largest. When the measurement light is irradiated for a short time, hemoglobin absorbs the measurement light and instantaneously expands to generate a pressure wave in the living body. The greater the amount of HbA1c, the greater the pressure wave. In addition, the pressure wave generated in the case of inside the blood vessel is larger than that in the case where the position where the intensity of the measurement light is the highest is outside the blood vessel, and this pressure wave is detected by the ultrasonic detector 30 as an ultrasonic wave.

  The detected ultrasonic signal is subjected to various processes in the ultrasonic signal processing unit 34 and input to the central processing unit 36 as a photoacoustic signal. The measurement unit 43 calculates the amount of HbA1c from the intensity of the photoacoustic signal. When the blood glucose concentration is measured, measurement light is irradiated from the light source 15d, and the glucose concentration is measured from the input photoacoustic signal. In this way, when measuring the HbA1c concentration or glucose concentration by photoacoustic spectroscopy, the level of the photoacoustic signal is increased, the S / N ratio is increased, and the accuracy is improved by narrowing the measurement light inside the blood vessel. High measurement can be performed.

  Next, a second embodiment will be described. Note that parts having the same configuration and operation as those of the first embodiment are denoted by the same reference numerals, and detailed description thereof is omitted. The blood information measuring device 50 includes an ultrasonic transducer 51 in the irradiation unit 20. Further, the ultrasonic transducer 51 can detect and emit ultrasonic waves from the subject by oscillating and irradiating ultrasonic waves by the ultrasonic input / output control unit 52. The light source unit 53 includes a light source 53a composed of a laser diode for AOT, and a light source 15b and a light source 15c for irradiating measurement light of 514 nm and 830 nm are provided for PAS as in the above embodiment. The ultrasonic modulation optical tomographic signal generation unit 54 extracts the light detected by the photodetector 19 as an ultrasonic modulation optical tomographic signal and sends it to the central processing unit 36.

  The operation of such blood information measuring apparatus 50 will be described. The measurement light emitted from the light source 53a passes through the fiber coupler 16 and enters the subject from the irradiation unit 20. The ultrasonic input / output control unit 52 irradiates the subject with ultrasonic waves from the ultrasonic transducer 51. The subject is irradiated with measurement light and ultrasonic waves. An acousto-optic effect is generated in the test portion irradiated with ultrasonic waves, and a refractive index distribution is formed by changes in the density of the living tissue. A part of the measurement light is refracted or diffracted by the acousto-optic effect, and is modulated by ultrasonic waves. The modulated measurement light returns to the irradiation unit 20 and is detected by the photodetector 19 as it is. The ultrasonic modulated optical tomographic signal generation unit 54 extracts the light detected by the photodetector 19 as an ultrasonic modulated optical tomographic signal and sends it to the central processing unit 36. The tomographic image generation unit 40 generates a tomographic image from the ultrasonic modulated optical tomographic signal.

  The blood vessel discriminating unit 41 obtains the blood vessel position and its depth from the tomographic image by image measurement. The focal position control unit 42 determines the focal position of the rod lens 28 from the obtained blood vessel position and depth. The rod lens driving unit 33 moves the rod lens 28. The system control unit 39 turns on the light source 15b and the light source 15c, and measures HbA1c by PAS. At this time, the ultrasonic input / output control unit 52 detects ultrasonic waves from the subject by the ultrasonic transducer 51. The detected ultrasonic signal is input to the central processing unit 36 as a photoacoustic signal. The measurement unit 43 measures the concentration of HbA1c based on the photoacoustic signal.

  As described above, the blood information measuring apparatus of the present invention can perform non-invasive measurement of blood vessel information using OCT, PAT, and AOT and blood glucose information using PAS. In particular, it is possible to increase the incident light density and obtain a strong photoacoustic signal by positioning the blood vessel at the focus of the measurement light. In the present invention, light having wavelengths of 514 nm and 830 nm is used. However, by using infrared light having a wavelength twice that of blood, blood glucose information is measured from a blood vessel at a deeper position in the living tissue. Also good. Further, in the present invention, the blood vessel may be discriminated based on the waveform of the detection signal by OCT, PAT, or AOT not accompanied by scanning, without being limited to specifying the blood vessel by performing image analysis from the tomographic image. For example, since the detection signal level for hemoglobin is high in PAT and the signal level is low in AOT, the blood vessel position may be specified from the strength of each signal level. Further, the present invention is not limited to HbA1c, and other glycated proteins may be measured.

It is a schematic block diagram of the blood information measuring device of a 1st embodiment. It is a flowchart of the blood information measuring device of a 1st embodiment. It is a schematic block diagram of the blood information measuring device of a 2nd embodiment. It is a flowchart of the blood information measuring device of 2nd Embodiment.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Blood information measuring device 11 Optical unit 12 Electric circuit unit 15 Light source part 15a, 15b, 15c, 15d Light source 16 Fiber coupler 17 Reference mirror 18 Optical path difference adjustment part 19 Photo detector 20 Irradiation part 21 Optical fiber 22 Piezo element 25 Condensing Lens 26 Driving Unit 27 Condensing Lens 28 Rod Lens 29 Reflecting Mirror 30 Ultrasonic Detector 33 Rod Lens Driving Unit 34 Ultrasonic Signal Processing Unit 35 Optical Tomographic Signal Generation Unit 36 Central Processing Unit 39 System Control Unit 40 Tomographic Image Generation Unit 41 Blood vessel discrimination unit 42 Focus position control unit 43 Measurement unit 45 Tomographic image display monitor 46 Region of interest setting unit 50 Blood information measurement device 51 Ultrasonic transducer 52 Ultrasonic input / output control unit 53 Light source unit 53a Light source 54 Ultrasonic modulation optical tomographic signal generation Part

Claims (4)

A blood vessel specifying means for specifying the position of the blood vessel;
Measurement light condensing means for condensing measurement light at the position of the specified blood vessel,
Photoacoustic signal detection means for detecting a sound pressure generated by an absorber in the blood that has absorbed the measurement light as a photoacoustic signal;
A blood information measuring device comprising blood glucose information measuring means for measuring blood glucose information in blood based on the photoacoustic signal. Comprising a tomographic signal generating means for generating a tomographic signal indicating tomographic information of a biological tissue,
The blood information measuring apparatus according to claim 1, wherein the blood vessel specifying means specifies a position of a blood vessel based on the tomographic information.   The blood information measuring apparatus according to claim 1 or 2, wherein at least one of glycated protein and glucose is measured as the blood glucose information. The blood information measuring apparatus according to any one of claims 1 to 3, wherein the measurement light includes two types of light having different wavelengths in order to generate two-photon absorption.

Images