JP2004167080A - Oxygen saturation degree measuring instrument - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an oxygen saturation degree measuring method and an oxygen saturation degree measuring instrument for dividing tissue containing blood components into micro regions and determining the oxygen saturation degree of the divided micro regions. <P>SOLUTION: This oxygen saturation degree measuring instrument is composed of a frequency variable coherent light source 1, a partial reflecting mirror 11, a reference mirror 12, an optical scanning system 2, a detector 3, an amplifier 4, an analog-to-digital converter 5, a data analysis system 6 and a sample 7 to be measured. The data analysis system 6 determines a light absorption coefficient in the micro regions along the beams of measuring light 14 by making a Fourier analysis of the accumulated data. Further, the light absorption coefficient is one-dimensionally computed while gradually increasing the depth in the beam direction along the beams of the measuring light 14, and then one-dimensional computation is repeated to perform two-dimensional computation to acquire a tomographic image on the amount of oxygenated hemoglobin, the amount of reduced hemoglobin, the total amount of hemoglobin and the degree of oxygen saturation. <P>COPYRIGHT: (C)2004,JPO

Description

[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to an oxygen saturation measuring method and an oxygen saturation measuring device for measuring the amount of oxygenated hemoglobin, the amount of reduced (free) hemoglobin, the amount of total hemoglobin, and the oxygen saturation of a living tissue for each minute region of the living tissue. .
[0002]
[Prior art]
Since the oxygen saturation of the blood component contained in the living tissue is important information for measuring the activity of the living tissue, many measuring methods have been tried in the past. For example, a method utilizing the fact that the light absorption coefficient, which is the degree of light absorption, depending on the wavelength of light differs between oxygenated hemoglobin and reduced hemoglobin.
[0003]
FIG. 8 is a graph showing changes in the light absorption coefficient of oxygenated hemoglobin and reduced hemoglobin with respect to the wavelength of light.
[0004]
As shown in FIG. 8, there is a difference in the wavelength dependence of the light absorption coefficient (molar light absorption coefficient) of oxygenated hemoglobin and reduced hemoglobin in the region from ultraviolet to visible light and infrared light. Several methods have been proposed for non-invasively determining the oxygen saturation by optical measurement using a plurality of wavelengths by utilizing the difference in the wavelength dependence of the light absorption coefficient.
[0005]
In such a method of non-invasively determining the oxygen saturation by optical measurement using a plurality of wavelengths using the difference in the wavelength dependence of the light absorption coefficient, if the light scattering ability of the tissue is weak, When the light propagates linearly while being absorbed, the light absorption coefficient per optical path length can be obtained from the attenuation rate of the transmitted light with respect to the incident light.
[0006]
However, in general, a living tissue has a high degree of light scattering, and light spreads while repeating multiple scattering, and propagates diffusely throughout the living body as a whole. For this reason, since the optical path length through which the light detected by the detector passes is not single but spreads out, it is difficult to obtain the light absorption coefficient per optical path length from the attenuation rate of the transmitted light with respect to the incident light. .
[0007]
In addition, since living tissue has strong light scattering ability, attenuation of light propagating through living tissue cannot be ignored not only in light absorption but also in light scattering. The problem is how to accurately derive the light absorption coefficient due to the blood component in the living tissue from the attenuation of the light that diffusely propagates while being attenuated by scattering.
[0008]
On the other hand, the light scattering ability decreases in inverse proportion to the fourth power of the wavelength. Therefore, in order to reduce the influence of the scattering, light having a long wavelength is advantageous. However, as the wavelength becomes longer than about 800 nm, light absorption by water contained in the living tissue increases (see FIG. 9).
[0009]
Therefore, in a method of non-invasively determining the oxygen saturation by optical measurement using a plurality of wavelengths using the difference in the wavelength dependence of the light absorption coefficient, oxygenated hemoglobin and reduced hemoglobin at a wavelength of about 800 nm are used. Utilizing the intersection of the light absorption coefficients (see FIG. 8), a wavelength range from 600 nm to 1000 nm from red to infrared is often used. However, in the case of eyes, visible light has been used in addition to infrared light because of its relatively weak scattering ability, which is close to that of a transparent body.
[0010]
Pulse oximetry is one of the methods for non-invasively determining the oxygen saturation by optical measurement using a plurality of wavelengths using the difference in the wavelength dependence of the light absorption coefficient.
[0011]
FIG. 10A is a principle diagram of pulse oximetry.
[0012]
Pulse oximetry measures the light absorption coefficient of arterial blood by separating the contribution of arterial blood to light absorption from other contributions using the pulsating effect of arteries.
[0013]
As shown in FIG. 10A, when a finger is interposed between the light source 81 and the detector, light is applied to the finger from the light source 81, and the transmitted light is detected by the detector 83, the intensity of the transmitted light becomes as shown in FIG. As shown, it has a component that varies slightly in response to the pulse. Since this fluctuation component (AC component) is caused by the blood vessel expanding and contracting due to the increase and decrease of the blood pressure due to the heartbeat, the degree of light absorption by the blood cells in the artery is detected, and the light of other parts is detected. Can be distinguished from absorption.
[0014]
Here, in consideration of the wavelength dependence of the light absorption coefficient in FIG. 8, two colors of red (for example, about 660 nm) and infrared (for example, 940 nm) are used as a light source, and oxygenated hemoglobin in blood and free (reduced) If the difference between the light absorption coefficient of each wavelength light source and hemoglobin is used, the oxygen saturation of arterial blood can be obtained. Although pulse oximetry is an excellent method for accurate measurements, it has the limitation that the subject is limited to arterial flow.
[0015]
As another method of non-invasively obtaining the oxygen saturation by optical measurement using a plurality of wavelengths using the difference in the wavelength dependence of the light absorption coefficient, a transcutaneous oxygen saturation concentration measurement device is used. is there,
FIG. 10B is a principle diagram of a transcutaneous oxygen saturation concentration measuring device.
[0016]
As shown in FIG. 10 (b), the transcutaneous oxygen saturation concentration measuring device determines a measurement site (for example, brain) of a target living tissue 82, uses two wavelengths (for example, 750 nm and 830 nm) as a light source, The structure of the probe 80 consisting of the light source 81 and the detector 83 is always the same according to the measurement site, the probe 80 is brought into close contact with the skin, the measurement is performed, and the oxygen saturation is determined by comparing with the calibration value which has been performed in advance. How to
[0017]
The transcutaneous oxygen saturation concentration measuring device is also called a non-invasive cerebral blood flow oxygen saturation monitor, particularly when the brain is targeted. This method has also been put to practical use in actual diagnosis. Since diffused transmitted light is used, the average value of the region where light is diffused can be obtained, but it is not possible to finely divide the measurement site and obtain the value of each section.
[0018]
As another method for non-invasively obtaining oxygen saturation by optical measurement using a plurality of wavelengths using the difference in wavelength dependence of the light absorption coefficient, a laser scanning method is used at a laboratory level. Has been done.
[0019]
The laser scanning method irradiates the fundus retina with a plurality of laser beams having different wavelengths, detects backscattered light using a conjugate optical system, and detects oxygen scattered at each wavelength along an optical path along the laser beam. This is a method for determining the degree of saturation.
[0020]
Here, measurement is performed by scanning the laser beam on the retina of the fundus. Compared to the above two methods, the measurement site is determined more accurately on a plane substantially perpendicular to the incident light, but the depth direction of the tissue along the incident light path is divided into minute regions, and the value of each of these divisions is obtained. It is not possible.
[0021]
[Patent Document 1]
JP-A-2002-303576
[0022]
[Patent Document 2]
JP-A-2002-2224088
[0023]
[Patent Document 3]
JP-A-11-244268
[0024]
[Problems to be solved by the invention]
As described above, in the prior art, in the case of pulse oximetry, the entire part of the finger irradiated with light, the entire region where light diffuses and propagates and reaches the detector in the transcutaneous oxygen saturation concentration measurement device, In the laser scanning method, all contributions from all tissues in the depth direction are measured. Therefore, according to the conventional technique, it is not possible to determine the oxygen saturation in each minute region of 1000 μm or less, for example, several μm to several tens μm inside the living tissue.
[0025]
The present invention has been made in view of the above problems, the tissue having a blood component is divided into small regions of about 1000 μm or less, for example, several μm to several tens μm, oxygenated hemoglobin concentration of the divided small regions, It is an object of the present invention to provide an oxygen saturation measurement method and an oxygen saturation measurement device for determining reduced hemoglobin concentration and oxygen saturation.
[0026]
[Means for Solving the Problems]
The oxygen saturation measurement method and the oxygen saturation measurement device according to the present invention irradiate light having two or more different wavelength regions to a tissue having a blood component, and in the region along the light beams, the backscattering of the irradiated light is performed. Measuring the intensity of light (including the case where it is reflected and scattered backward due to a rapid change in the refractive index) by discriminating in the light beam direction into a minute area of about 1 to 1000 μm; Determining the light absorption coefficient of the light in the minute region for each wavelength region from the intensity of the backscattered light from the minute region before and after the minute region in the light beam direction, which is measured for the light in the above wavelength region; From the light absorption coefficient value in the region, utilizing the fact that the wavelength dependence of the light absorption coefficient differs between oxygenated hemoglobin and reduced hemoglobin, the oxygenated hemoglobin in the minute region is used. Down amount, reduced hemoglobin, and having the steps of: determining at least one of total hemoglobin or oxygen saturation
As described above, according to the oxygen saturation measurement method and the oxygen saturation measurement apparatus according to the present invention, the tissue having the blood component is discriminated into the minute regions, and the backscattered light intensity is measured in two or more wavelength regions. Therefore, the light absorption coefficient of each minute region can be obtained in a plurality of light wavelength regions. Then, by associating these light absorption coefficients with the difference in wavelength dependence of the light absorption coefficients of oxygenated hemoglobin and reduced hemoglobin, oxygenated hemoglobin, reduced hemoglobin, total hemoglobin amount and Oxidation saturation can be determined.
[0027]
BEST MODE FOR CARRYING OUT THE INVENTION
[Principle of the invention]
A beam of light is incident on the object to be measured, and the intensity of backscattered light from two adjacent regions in the depth direction along the incident light (or a case where a plurality of regions are used is included) is measured by discriminating a place where the light is scattered. I do. Then, by evaluating the influence of light absorption by the blood component in the minute region between the measured regions from these measurement data, the blood in the minute region can be accurately detected without being affected by the tissue in other regions. Can be obtained. If this is performed using two or more wavelengths and the light absorption coefficient of the minute area due to blood is determined, the light absorption coefficient is determined at a plurality of light wavelengths. By associating these light absorption coefficients with the differences in the wavelength dependence of the light absorption coefficients of oxygenated hemoglobin and reduced hemoglobin shown in FIG. 8, the amounts of oxygenated hemoglobin and reduced hemoglobin can be determined, and the oxidation saturation Can be determined for a minute area.
[0028]
Here, optical coherence tomography (hereinafter referred to as OCT) is used as a means for measuring the light backscattered from a region of several microns to several tens of microns along the ray of incident light by discriminating the place where the light is backscattered. To use) technology.
[0029]
OCT measures only a component of the backscattered light that interferes with the incident light. Therefore, in the multiple scattering that propagates in a diffuse manner, the in-phase plane of light is disturbed, so that the interference is weakened, and the influence of the multiple scattering is almost negligible or can be ignored. Therefore, the light path in the sample in OCT may be regarded as a straight line. Hereinafter, it is assumed that the multiple scattering component does not contribute to the interference.
[0030]
In OCT, a light source having a wide wavelength range is used. Therefore, strictly speaking, it is necessary to consider the wavelength spread in the optical characteristics. However, since the width of the spread of the wavelength is less than about 10% of the central wavelength, the central wavelength is represented in the following description.
[0031]
FIG. 12 is a diagram showing a principle of measuring a light absorption coefficient in a minute region.
[0032]
In FIG. 12, it is assumed that a light beam having a center wavelength λ for measurement is incident along the Z axis in the depth direction. OCT measures light that is backscattered in the opposite direction to the incident light along the incident light path at intervals of several microns to several tens of microns on the Z axis. One measurement point is z, and a measurement point in the depth direction of a small distance Δz from this is z + Δz. Here, it is assumed that the scattering power is the same at both points, and the light is attenuated only by the absorption by hemoglobin.
[0033]
If the light absorption coefficient in a minute area from position z to z + Δz along the ray of the incident light (Z axis) is represented by μ (z, λ) as a function of the position z and the center wavelength λ, the measurement light at the position z The ratio between the intensity I (z) and the measured light intensity I (z + Δz) at the position z + Δz is I (z) / I (z + Δz) = exp [2μ (z, λ) according to the Beer-Lambert law of light absorption. Δz]. Here, the coefficient 2 is due to light reciprocating on this path. If this logarithm is obtained and divided by 2Δz, the light absorption coefficient μ (z, λ) at the wavelength λ in the range of z + Δz from the minute area z is obtained.
[0034]
Conventionally, OCT is performed at one center wavelength, but in the present invention, two or more center wavelengths λ₁, Λ₂, Λ₃, ... Increasing the number of wavelength types increases the number of parameters that can be determined and increases accuracy, but here, for simplicity, λ₁And λ₂The case of measurement at two wavelengths will be described. The wavelength dependence of the light absorption coefficient differs between oxygenated hemoglobin and reduced hemoglobin as shown in FIG. For example, λ₁= 750 nm, λ₂= 850 nm, λ₁= 750 nm, the reduced hemoglobin has a larger light absorption coefficient, which is almost identical at 800 nm, and₂At = 850 nm, oxygenated hemoglobin has a larger light absorption coefficient.
[0035]
The concentrations of oxygenated hemoglobin and reduced hemoglobin at the position z on the Z-axis are represented by C_HbO(Z), C_Hb(Z). Wavelength λ₁And λ₂The light absorption coefficients of oxygenated hemoglobin and reduced hemoglobin at the above are given in FIG._HbO  (Λ₁), Μ_Hb(Λ₁) Μ_HbO  (Λ₂), Μ_Hb (Λ₂). The concentration and light absorption coefficient are compared with the actually measured light absorption coefficient μ (z, λ₁), Μ (z, λ₂) And the following relational expression holds.
μ_HbO  (Λ₁) ・ C_HbO(Z) + μ_Hb(Λ₁) ・ C_Hb(Z) = μ (z, λ₁(1)
μ_HbO  (Λ₂) ・ C_HbO(Z) + μ_Hb(Λ₂) ・ C_Hb(Z) = μ (z, λ₂(2)
By solving this simultaneous equation, the oxygenated hemoglobin concentration C in the minute region at the position z_HbO(Z), reduced hemoglobin concentration C_Hb(Z) are obtained, and the total hemoglobin amount [C_HbO  (Z) + C_Hb(Z)] is obtained, and the oxygen saturation is also expressed by the formula: (oxygen saturation) = (oxygenated hemoglobin amount) / [(oxygenated hemoglobin amount) + (reduced hemoglobin amount)] = C_HbO  (Z) / [C_HbO  (Z) + C_Hb(Z)]. In this method, a light absorption coefficient is obtained based on the intensity of the backscattered light immediately before and immediately after the narrow range Δz of several microns to several tens of microns at the position z in the tissue, and the oxygen saturation is determined from these values. , A very detailed and accurate measurement of oxygen saturation can be made.
[0036]
In this way, it is possible to measure the oxygen saturation of a minute region inside the living tissue, which was impossible with the pulse oximetry, the transcutaneous oxygen saturation concentration measuring device, and the laser scanning method, which are conventional techniques.
[0037]
For example, a vein near the surface of a tissue can be distinguished from an artery located deep in the tissue, and the oxygen saturation and the like of each blood vessel can be measured.
[0038]
One-dimensional measurement (referred to as A-scan) is performed while gradually increasing the value of z along the ray (Z-axis) of the incident light, and the incident light is scanned and one-dimensional measurement is repeated one after another to perform two-dimensional measurement (B (Referred to as scanning), a tomographic image of the amount of oxygenated hemoglobin, the amount of reduced hemoglobin, the total amount of hemoglobin, and the oxygen saturation is obtained. If a plurality of two-dimensional measurements are taken by scanning and displayed side by side, a three-dimensional tomographic image can be obtained three-dimensionally. Displaying a two-dimensional or three-dimensional tomographic image is useful for elucidating the biological activity inside a tissue.
[0039]
Above, the absorption was dominant, the attenuation of light due to scattering was negligible, and the scattering intensity was constant. For the case of using the measurement of two wavelengths for the tissue, the wavelength was described as an example. If the amount of absorption is not negligible, if the attenuation of light due to light scattering is not negligible, or if the backscattering power varies from place to place, the number of parameters to be determined increases. In such a case, the number of wavelengths to be measured may be increased to determine those parameters.
In addition, using four wavelengths (for example, 775 nm, 810 nm, 870 nm, and 904 nm), an algorithm for simultaneously determining the amount of cytochrome c / oxidase (cyt-aa3) in addition to reduced hemoglobin and oxygenated hemoglobin is adopted. The impact of the system can also be evaluated.
[0040]
Here, the principle of the present invention has been described by taking OCT, for example, in which the technology is currently established, but the present invention is more generally applicable to a technology for measuring an optical tomographic image, and is a device using OCT. However, the present invention is not limited to this.
[0041]
Also, a case where measurement is performed at two wavelengths using specific wavelength values is shown here, but this is an example for simplifying the description, and does not limit the scope of the invention.
[0042]
Furthermore, the same result as described above can be obtained by analyzing optical tomographic image data already obtained elsewhere without performing measurement.
Next, an embodiment of the present invention will be described in detail with reference to FIGS.
[0043]
The embodiment of the present invention can be applied to any apparatus that optically measures living tissue in one-dimensional, two-dimensional, or three-dimensional tomographic manner. Among these various optical tomographic imaging methods, OCT is a method particularly suitable for implementing the present invention, and an embodiment using OCT will be described below.
[0044]
[First Embodiment]
OCT mainly includes i) optical frequency domain reflectometry (OFDR), ii) optical coherence domain reflectometry (OCDR), iii) spectral interferometer (SI) ) There are three methods.
[0045]
In the first embodiment, an OFDR method (Optical Frequency Domain Reflectometry method) is used from among the above three methods as an apparatus that optically measures a biological tissue in one-dimensional, two-dimensional, or three-dimensional tomography. Is the way.
[0046]
FIG. 1 is a principle diagram of the oxygen saturation measuring device according to the first embodiment.
[0047]
As shown in FIG. 1, the oxygen saturation measuring apparatus of the present embodiment uses a Michelson interferometer as an optical multiplexer / demultiplexer, and includes a frequency-variable coherent light source 1, a partial reflection mirror 11, and a reference mirror 12 , An optical scanning system 2, a detector 3, an amplifier 4, an A / D converter 5, a data analysis system 6, and a sample 7 to be measured.
[0048]
The variable frequency coherent light source 1 can oscillate light having coherence and change the wavelength of the oscillated light discretely or continuously over time. In this case, the light interference length must be longer than the entire length of the sample to be measured.
[0049]
The partial reflection mirror 11 has a function as an optical multiplexing unit. That is, the light emitted from the variable frequency coherent light source 1 is divided by the partial reflection mirror 11 into the reference light 13 reflected by the partial reflection mirror 11 and the measurement light 14 transmitted through the partial reflection mirror 11. The reference light 13 is reflected by the reference mirror 12 and returns to the partial reflection mirror 11. The measurement light 14 is incident on the sample 7 via the optical scanning system 2, and the light backscattered everywhere on the light beam of the incident light in the sample 7 returns to the partial reflection mirror 11 along an opposite path. The returned backscattered light and the reference light 13 reflected by the reference mirror 12 are combined by the partial reflection mirror 11, and the combined signal is input to the detector 3 as an interference signal.
[0050]
The optical scanning system 2 causes the measurement light 14 to enter the sample 7 while being slightly shifted in direction so that the light beam of the measurement light 14 incident on the sample 7 forms a constant surface. As described above, the direction of incidence of the measurement light 14 on the sample 7 is slightly shifted by the optical scanning system 2, and the data of the backscattered light along the light beam incident on each direction is acquired. Data for obtaining a tomographic image of the image data.
[0051]
Here, the optical path from the frequency-variable coherent light source 1 reflected by the partial reflection mirror 11, further reflected by the reference mirror 12, and input again to the detector 3 via the partial reflection mirror 11 is referred to as a reference optical path. The light passes through the partial reflection mirror 11 from the variable frequency coherent light source 1, is incident on the sample 7 via the optical scanning system 2, is scattered back by the sample 7, returns to the partial reflection mirror 11, returns to the partial reflection mirror 11, and is partially reflected. The optical path up to the input to the detector 3 via the mirror 11 is called a sample optical path.
[0052]
The interference signal multiplexed by the partial reflection mirror 11 through the reference optical path and the sample optical path is detected by the detector 3, amplified by the amplifier 4, digitized by the A / D converter 5, and digitized. Are successively accumulated in the data analysis system 6 as data.
[0053]
The data analysis system 6 has a function as signal analysis means. That is, by performing Fourier analysis on the accumulated data, the intensity of the backscattered light from the sample 7 in the form corresponding to the depth in the depth direction of the sample 7 is determined by the depth in the light direction of the measurement light 14 incident on the sample 7. As a function of From the intensity of the backscattered light obtained in this way, the light absorption coefficient in a minute area along the light beam of the measurement light 14 incident on the sample 7 is obtained. Further, based on data obtained by sequentially changing the direction of incidence of the measurement light 14 on the sample 7, the light absorption coefficient in a small area along the light beam of the measurement light 14 in each direction is obtained, and these data are accumulated. Data of the light absorption coefficient in each minute region of the predetermined cross section of the sample 7 is obtained.
[0054]
Further, the data analysis system 6 calculates the amount of oxygenated hemoglobin, the amount of reduced hemoglobin, and the amount of total hemoglobin from the data of the light absorption coefficient in the minute region obtained in two or more wavelength regions by the method described in the principle of the invention. Obtain tomographic images for the amount and oxygen saturation. Further, if two-dimensional measurement is repeated while shifting the measurement cross section of the sample 7 little by little and displayed side by side, a three-dimensional tomographic image can be obtained three-dimensionally.
[0055]
Next, a method for determining the relationship between the intensity of the backscattered light from the sample 7 and the depth of the measurement light 14 incident on the sample 7 in the light beam direction and the wavelength of the measurement light 14 in the data analysis system 6 will be described.
[0056]
For simplicity, the reciprocal of the wavelength of the light source is 1 / λ_sFrom 1 / λ_eLet's consider a case where measurement is performed by changing the value to At this time, the center wavelength is λ_c= | Λ_s+ Λ_e| / 2.
[0057]
Here, the difference between the optical distance from the partial reflection mirror 11 to the reference mirror 12 and the optical distance from the partial reflection mirror 11 to an arbitrary measurement position on the sample to be observed is Z. Since the position of the reference mirror 12 has a function of determining the measurement reference point, for example, if the position of the reference mirror 12 is adjusted here, when the measurement light 14 is incident on the sample 7, Z is incident. It can be regarded as an optical distance from a point to a minute area scattered backward.
[0058]
When the wavelength of the light output from the frequency variable coherent light source 1 is λ, the backscattered light at a distance Z from the point where the measurement light 14 is incident on the sample 7 and the reference light reflected from the reference mirror 12 are combined. Assuming that the intensity of the waved interference signal (hereinafter referred to as measurement light intensity) is As, As is a function of λ and Z,
As∝cos (4πZ / λ) (3)
Is represented by
Here, the wavelength λ of the light output from the frequency-variable coherent light source 1 is 1 / λ at the same light intensity._sFrom 1 / λ_e2A, the detector 3 can measure the measurement light intensity as a function of the reciprocal of the light source λ, as shown in FIG.
[0059]
However, what is actually measured by the detector 3 is the measurement light intensity from all points along the light beam of the measurement light 14, that is, the value obtained by continuously changing Z in the depth direction in Expression (3), Are superimposed. That is, it is measured directly by the detector 3.
The information on the distance Z in the depth direction of the sample 7 does not appear on the surface of the signal.
[0060]
Therefore, in order to determine the relationship between the intensity of the backscattered light from the sample 7 and the depth of the measurement light 14 incident on the sample 7 in the light beam direction, first, the measurement light intensity As is calculated based on the data measured by the detector 3. By multiplying by cos (4πX / λ) and integrating with respect to (1 / λ), a Fourier component As ′ having an intensity proportional to As at X = Z is obtained. This may be considered as the measured light intensity As' when the distance Z in the depth direction of the sample 7 is X.
[0061]
Here, if the above integration is performed while changing the value of X, the measured light intensity As' at any position in the depth direction along the light beam of the sample 7 can be obtained.
[0062]
However, information on the wavelength λ of the measurement light 14 does not appear on the surface in the value obtained here. However, here, the wavelength λ of light is 1 / λ at the same light intensity._sFrom 1 / λ_eThe measured light intensity As' obtained here is obtained by integrating (1 / λ) with respect to the value measured and changed to 1 / λ._sAnd 1 / λ_eThe central value of 1 / λ_cMay be considered as the measurement light intensity As'.
[0063]
In this way, for the backscattering by the tissue, the measurement light intensity As' ([lambda]) while gradually increasing the value of z along the ray of the incident light (Z-axis)._c, Z) can be calculated one-dimensionally, and the tomographic signal in the one-dimensional direction has a center wavelength λ._cIs obtained.
[0064]
The obtained As ′ (λ_c, Z) indicates that the wavelength of the measuring light 14 is the center wavelength λ._cIn this case, it can be considered as the backscattering intensity from the sample 7 at the position z on the light beam. In this case, the intensity of the backscattering light of the measuring light 14 irradiating the sample 7 was measured by discriminating it into a minute area in the beam direction. Will be.
[0065]
The thus obtained As ′ (λ_c, Z), As ′ (λ at z) according to the procedure described in the principle of the invention described above._c, Z) and As ′ (λ at z + Δz)_c, Z + Δz)), the wavelength λ in the region of position z and width Δz according to the Beer-Lambert law of light absorption._cLight absorption coefficient μ (λ_c, Z) are required.
[0066]
In order to determine the oxygen saturation from the light absorption coefficient, it is necessary to determine the light absorption coefficient in a plurality of wavelength regions of two or more wavelengths. Here, analysis is performed by dividing the wavelength range of a series of measurements. In the present embodiment, as shown in FIGS. 2A and 2B, when the wavelength range of the measurement light 14 output from the frequency-variable coherent light source 1 extends around 800 nm, one The area is λ_sTo λ_se(<800 nm) and the center wavelength is λ_c1= (Λ_se―Λ_s) / 2 and the other is λ_es(> 800 nm) to λ_eAnd the center wavelength λ_c2= (Λ_e−λ_es) / 2. If the analysis is performed separately for each wavelength region, the light absorption coefficient at the position z of the sample 7 in each wavelength region can be obtained. From the measured value of the light absorption coefficient in these two wavelength regions and the wavelength dependence of the light absorption coefficient shown in FIG. 8, the amount of oxygenated hemoglobin at the position z and the reduced hemoglobin at the position z are determined in the same manner as described in the principle of the invention. The amount and oxygen saturation are determined.
[0067]
Note that, here, an example in which a light source near 800 nm is used and the wavelength region is divided into two regions for analysis has been described, but the present invention includes a case where the wavelength region is performed in any wavelength region from ultraviolet to infrared, Also, the number of divisions of the wavelength region includes the case of all three or more.
[0068]
In FIG. 1, the reference light path is separated from the sample light path by the partial reflection mirror 11, but since the length of the reference light path and the length of the sample light path may be different, as shown in FIG. May not be separated from the sample optical path, and the partial reflection mirror 13 may be placed in the sample optical path. In addition, the reflection mirror 13 may be removed from FIG. 3, and the strong reflection light of a part of the sample may be used as the reference light without using the reflection mirror 13. Alternatively, mutual interference of backscattered light from each part of the sample may be used.
[0069]
Further, as another method, a Mach-Zehnder interferometer can be used as shown in FIG.
[0070]
FIG. 1 shows a case in which light rays propagate in the air and optical elements arranged in the air are used for the optical paths and the optical components constituting the present embodiment so that the functions of the respective components can be easily understood. However, in order to form a more stable optical system, an optical fiber optical system is more suitable. Therefore, it is needless to say that the optical fiber optical system may be partially or entirely used in FIG.
[0071]
As the frequency-variable coherent light source 1, various light sources can be used, such as taking out light with good coherence using various optical filters from a light source having a wide spectrum such as a semiconductor laser having an external resonance or a superluminescent diode. . In the present embodiment, all these cases are included irrespective of the type of the light source, such as the case of these light sources or the light source combining them.
[0072]
In addition, as a method of irradiating and detecting light from the frequency-variable coherent light source 1, a thin light beam is irradiated on the sample 7, received by the detector 3 at one point, measured one-dimensionally, and subjected to one-dimensional tomography in the depth direction. An image is obtained, then a light beam is scanned to obtain one-dimensional tomographic images one after another, and these are combined to obtain a two-dimensional tomographic image. As shown in FIG. Alternatively, the light may be received by a two-dimensional detector, and the received light intensity of each pixel of the two-dimensional detector may be analyzed to obtain a three-dimensional tomographic image.
[0073]
References relating to the OFDR method OCT technology include “Handbook of Optical Coherence Tomography” edited by B.C. E. FIG. Bouma and G .; J. Tearney, pp. 359-384 and the like.
[0074]
As described above, according to the first embodiment, the backscattered light intensity is scattered from two adjacent minute regions (or including a case where a plurality of minute regions are used) in the depth direction along the measurement light 14. Measure the location where it was received. Then, based on these measurement data, the influence of light absorption by the blood component in the minute region between the measured regions is evaluated, so that the blood in the minute region is accurately measured with little influence from the tissue in other regions. The light absorption coefficient can be determined.
[0075]
Then, the measurement is performed using two or more wavelength regions, and the light absorption coefficient of blood in the minute region is obtained. Therefore, the light absorption coefficient can be obtained in a plurality of wavelength regions. The oxygenated hemoglobin, reduced hemoglobin, total hemoglobin amount, and oxidative saturation in each microregion in the tissue are determined by associating the difference in the wavelength dependence of the light absorption coefficient between oxygenated hemoglobin and reduced hemoglobin shown in FIG. can do. Further, the result can be displayed as a tomographic image.
[0076]
Further, since the measurement is performed by scanning the frequency of the light emitted from the variable frequency coherent light source 1, it is possible to oscillate the light by selecting a wavelength region suitable for carrying out the present invention, and to carry out the present invention optimally.
[0077]
In addition, since the intensity of the backscattered light from a specific position on the light beam is measured by using the Fourier analysis technique, the measurement can be performed with the reference mirror 12 fixed, and no mechanical movable part is required. Therefore, precise measurement can be easily performed.
[0078]
[Second embodiment]
The second embodiment is a method that uses an OCDR (Optical Coherence Domain Reflectometry) method as an apparatus that optically measures a biological tissue in one-dimensional, two-dimensional, or three-dimensional tomography.
[0079]
FIG. 6 is a principle diagram of the oxygen saturation measuring device according to the second embodiment.
[0080]
As shown in FIG. 6, the oxygen saturation measuring apparatus of the present embodiment uses an optical fiber as an optical path and an optical component, and includes a short coherent long light source 61, an optical multiplexer / demultiplexer 64, and a reference mirror. 12, an optical scanning system 62, a detector 63, an amplifier 65, an A / D converter 66, a data analysis system 67, and a sample 7 to be measured.
[0081]
The short coherent length light source 61 oscillates light having a short coherent length (several μm to several tens μm). In this case, the shorter the coherent length of the light, the higher the resolution of the measurement light.
[0082]
That is, the oxygen saturation measuring apparatus according to the second embodiment is separated from the short coherent long light source 1 by the optical multiplexer / demultiplexer 64, further reflected by the reference mirror 12, and passed through the optical multiplexer / demultiplexer 64 again. The length of the reference optical path up to the input to the detector 63 and the light transmitted through the optical multiplexer / demultiplexer 64 from the short coherent length light source 61, are incident on the sample 7 via the optical scanning system 62, and are backscattered by the sample 7. The optical multiplexer / demultiplexer 64 returns to the optical multiplexer / demultiplexer 64 by following the reverse path, and when the length of the measurement optical path from the time when the light is multiplexed to the time when it is input to the detector 63 coincides, strong optical interference occurs. This utilizes the fact that the degree of intensity modulation applied to the multiplexed light is increased.
[0083]
In other words, if the position of the reference mirror 12 is changed, the length of the reference optical path is changed. Therefore, the light is backscattered from a specific position of the sample 7 corresponding to the position after the change of the reference mirror 12. The degree of modulation intensity to be performed becomes large. In this way, it can be distinguished from the backscattered light from other positions. In addition, by gradually moving the position of the reference mirror 12, it is possible to measure the intensity of the backscattered light at any position along the light ray direction of the sample 7.
[0084]
The light emitted from the short coherent long light source 61 is introduced into an optical multiplexer / demultiplexer 64, and is separated into the reference light 13 and the measurement light 14 by the optical multiplexer / demultiplexer 64. The reference light 13 is reflected by the reference mirror 12 that moves back and forth in the light beam direction of the reference light in the distance range according to the measurement range of the sample, and returns to the optical multiplexer / demultiplexer 64. The measurement light 14 is incident on the sample 7 via the optical scanning system 2, and the light backscattered at any place on the light beam of the incident light in the sample 7 returns to the optical multiplexer / demultiplexer 64 along the reverse path. . The returned backscattered light and the reference light 13 reflected by the reference mirror 12 are multiplexed by an optical multiplexer / demultiplexer 64, and the multiplexed signal is input to a detector 63 as an interference signal.
[0085]
Here, as a movement pattern of the reference mirror 12, in order to facilitate processing in the analysis system, the movement from the start point to the end point of the distance range is performed at a constant speed, and then the speed is returned to the start point at a high speed. A pattern (sawtooth, triangular pattern) having a time zone in which the reflector moves at a constant speed is used.
[0086]
The optical scanning system 62 causes the measuring light 14 to enter the sample 7 while being slightly shifted in direction so that the light beam of the measuring light 14 incident on the sample 7 forms a constant surface. As described above, the direction in which the measurement light 14 is incident on the sample 7 is slightly shifted by the optical scanning system 62, and the data of the backscattered light along the light beam incident in each direction is acquired. A tomographic image of the oxygen saturation and the like can be obtained.
[0087]
The signal multiplexed by the optical multiplexer / demultiplexer 64 through the reference optical path and the sample optical path is detected by the detector 63, amplified by the amplifier 65, digitized by the A / D converter 66, and digitized. Is input to the data analysis system 67 as data.
[0088]
The data analysis system 67 determines the correspondence between the degree of intensity modulation applied to the light multiplexed by the optical multiplexer / demultiplexer 64 and the position of the reference mirror 12 (for the portion where the measurement light is introduced). A process of obtaining optical characteristic data at several places having different depths in the light beam direction) to obtain the intensity of the backscattered light from the sample 7 and the light direction Seek relationship with depth. From the intensity of the backscattered light obtained in this way, a light absorption coefficient in a minute area along the light beam of the measurement light 14 incident on the sample 7 is obtained, and the result is stored.
[0089]
In this way, by moving the reference mirror 12, the position of the measurement point of the backscattered light is gradually increased along the light beam of the measurement light 14 in the light beam direction, and one-dimensional measurement is performed. That is, the tomographic image of the light absorption coefficient is obtained from the obtained data of the light absorption coefficient in the minute area by sequentially changing the incident direction. Further, if two-dimensional measurement is repeated while shifting the measurement cross section of the sample 7 little by little and displayed side by side, a three-dimensional tomographic image can be obtained three-dimensionally.
[0090]
Further, the data analysis system 67 performs measurement at two center wavelengths, obtains a light absorption coefficient in each minute region inside the sample at each wavelength, and performs oxygen absorption in this minute region by the procedure described in the principle of the present invention. The amount of modified hemoglobin, the amount of reduced hemoglobin, the amount of total hemoglobin, and the oxygen saturation are determined.
[0091]
In the second embodiment, a light source that emits short coherent long light is used. The spectrum of this light source has a center wavelength λ._cThe spectrum width is about 10% of the above, and the resolution increases as the spectrum width increases. In the present embodiment, for example, a wavelength shorter than 800 nm (λ_{c 1}) And long wavelength (λ_{c 2}) Is measured at the two central wavelengths, the light absorption coefficient in each minute region inside the sample is determined at each wavelength, and the amount of oxygenated hemoglobin, the amount of reduced hemoglobin, the amount of total hemoglobin, and the oxygen saturation in this minute region are determined. .
[0092]
In the present embodiment, a plurality of devices having different wavelengths as center wavelengths may be used to determine the amount of oxygenated hemoglobin, the amount of reduced hemoglobin, the amount of total hemoglobin, and the degree of oxygen saturation in the minute region based on the acquired data. good.
[0093]
In addition, although there is only one apparatus, a light source that generates two or more different center wavelengths is used, and the light source is sequentially changed and alternately performed to perform oxygenated hemoglobin amount, reduced hemoglobin amount, total hemoglobin amount, and The oxygen saturation may be determined.
[0094]
Furthermore, a single device uses a light source that simultaneously generates short coherent long light at a plurality of center wavelengths, separates and simultaneously measures with a detection system using a difference in modulation frequency, and oxygenates hemoglobin in a minute area. The amount, reduced hemoglobin amount, total hemoglobin amount and oxygen saturation may be determined.
[0095]
Also in this embodiment, in addition to the method using fiber optics shown in FIG. 6, a method using bulk optics similar to FIG. 1 in the first embodiment, and a Mach-Zehnder interference similar to FIG. Needless to say, a method using a meter, a method using a two-dimensional detector similar to FIG. 5, and the like are possible.
[0096]
References regarding the OCDR method OCT include D.C. Huang et al. , "Optical Coherence Tomography", Science 1991, 254, pp. 146-64. 1178-1181 and the like.
[0097]
As described above, according to the second embodiment, the backscattered light intensity is scattered from two adjacent minute regions (or including a case where a plurality of minute regions are used) in the depth direction along the light beam of the measurement light 14. Measure the location where it was received. Then, based on these measurement data, the influence of light absorption by the blood component in the minute region between the measured regions is evaluated, so that the blood in the minute region is accurately measured with little influence from the tissue in other regions. The light absorption coefficient can be determined.
[0098]
Then, the measurement is performed using two or more wavelength regions, and the light absorption coefficient of blood in the minute region is obtained. Therefore, the light absorption coefficient can be obtained in a plurality of wavelength regions. The oxygenated hemoglobin, reduced hemoglobin, total hemoglobin amount, and oxidative saturation in each microregion in the tissue are determined by associating the difference in the wavelength dependence of the light absorption coefficient between oxygenated hemoglobin and reduced hemoglobin shown in FIG. can do. Further, the result can be displayed as a tomographic image.
[0099]
Further, since a short coherent long light source is used, the range of light source selection is widened. Further, the resolution can be increased by shortening the coherent length.
[0100]
[Third Embodiment]
The third embodiment is a method using an SI (Spectral Interferometer) method as an apparatus for optically measuring a biological tissue in one-dimensional, two-dimensional, or three-dimensional tomography.
[0101]
FIG. 7 is a principle diagram of the oxygen saturation measuring device according to the third embodiment.
[0102]
As shown in FIG. 7, the oxygen saturation measuring apparatus according to the present embodiment includes a short coherent long light source 71, a partial reflection mirror 11, an optical scanning system 72, a spectral system 73, an array detector 74, an amplifier 75, an A / D. It comprises a converter 76, a data analysis system 77 and a sample 7 to be measured.
[0103]
As the light source, a short coherent long light source 71 is used as in the second embodiment. Light emitted from the short coherent long light source 71 passes through the partial reflection mirror 11 and is incident on the sample 7 as the measurement light 14 via the optical scanning system 72. The measuring light 14 is backscattered everywhere on the light beam of the incident light in the sample 7 and returns to the partially reflecting mirror 11 along the reverse path. The returned backscattered light is reflected by the partial reflection mirror 11 and is input to the spectroscopy system 73.
[0104]
The optical scanning system 72 shifts the direction of the measurement light 14 little by little so that the light beam of the measurement light 14 incident on the sample 7 forms a constant surface, and causes the measurement light 14 to enter the sample 7. In this way, the direction of incidence of the measurement light 14 on the sample 7 is slightly shifted by the optical scanning system 2 to acquire data of backscattered light along rays incident on each direction. A tomographic image of the oxygen saturation and the like can be obtained.
[0105]
Since the short coherent long light is light having a spread in wavelength, a band-like spectrum can be observed when the light is separated by the spectroscopic system 73. The light split by the spectroscopy system 73 is applied to the array detector 74, and the entire spectrum is simultaneously measured. The signal received by each element of the array detector 74 is transferred to the data analysis system 77 via the amplifier 75 and the A / D converter 76.
[0106]
The data analysis system 77 performs a Fourier analysis on the obtained data in the same procedure as in the first embodiment, and generates a tomographic image of the light absorption coefficient in a minute area along the light beam of the measurement light 14 incident on the sample 7. obtain.
[0107]
Furthermore, measurement was performed in a wavelength region of two or more wavelengths. One-dimensional measurement is repeated one after another to perform two-dimensional measurement, thereby obtaining a tomographic image of the amount of oxygenated hemoglobin, the amount of reduced hemoglobin, the total amount of hemoglobin, and the oxygen saturation. Further, if two-dimensional measurement is repeated while shifting the measurement cross section of the sample 7 little by little and displayed side by side, a three-dimensional tomographic image can be obtained three-dimensionally.
[0108]
As shown by a dotted line in FIG. 7, the signal strength may be improved by a heterodyne effect by using a reference optical path by adding a reference mirror 12.
[0109]
References relating to the OFDR method OCT technology include “Handbook of Optical Coherence Tomography” edited by B.C. E. FIG. Bouma and G .; J. Tearney, pp. 359-384 and the like.
[0110]
As described above, according to the third embodiment, the backscattered light intensity is scattered from two adjacent minute regions (or including a case where a plurality of minute regions are used) in the depth direction along the light beam of the measurement light 14. Measure the location where it was received. Then, based on these measurement data, the influence of light absorption by the blood component in the minute region between the measured regions is evaluated, so that the blood in the minute region is accurately measured with little influence from the tissue in other regions. The light absorption coefficient can be determined.
[0111]
Then, the measurement is performed using two or more wavelength regions, and the light absorption coefficient of blood in the minute region is obtained. Therefore, the light absorption coefficient can be obtained in a plurality of wavelength regions. The oxygenated hemoglobin, reduced hemoglobin, total hemoglobin amount, and oxidative saturation in each microregion in the tissue are determined by associating the difference in the wavelength dependence of the light absorption coefficient between oxygenated hemoglobin and reduced hemoglobin shown in FIG. can do. Further, the result can be displayed as a tomographic image.
[0112]
Furthermore, since the light generated simultaneously from the short coherent long light sources having a plurality of different center wavelengths can be simultaneously decomposed by the spectroscopic system, tomographic images in the depth direction at different wavelengths can be simultaneously measured.
[0113]
【The invention's effect】
As described above, according to the oxygen saturation measurement method and the oxygen saturation measurement apparatus according to the present invention, the tissue to be measured is divided into small regions of 1000 μm or less, for example, several μm to several tens μm, and the tissue is divided. The oxygenated hemoglobin concentration, the reduced hemoglobin concentration, and the oxygen saturation of the minute region can be determined.
[Brief description of the drawings]
FIG. 1 is a principle diagram of an oxygen saturation measuring apparatus according to a first embodiment.
FIG. 2A is a diagram showing data of backscattered light intensity obtained by changing the frequency of measurement light. FIG. 2B is a diagram showing data of the backscattered light intensity obtained by performing a Fourier analysis on this.
FIG. 3 is a principle diagram of an oxygen saturation measuring device in which a partial reflection mirror 13 is placed in a sample optical path.
FIG. 4 is a principle diagram of an oxygen saturation measuring device using a Mach-Zehnder interferometer.
FIG. 5 is a principle diagram of an oxygen saturation measuring device that irradiates a sample with light in a plane.
FIG. 6 is a principle diagram of an oxygen saturation measuring apparatus according to a second embodiment.
FIG. 7 is a principle diagram of the oxygen saturation measuring apparatus according to the first embodiment.
FIG. 8 is a diagram showing the relationship between the light absorption coefficient of oxygenated hemoglobin and reduced hemoglobin with respect to the wavelength of light.
FIG. 9 is a diagram showing a light absorption coefficient by water contained in a living tissue.
FIG. 10 (b) is a principle diagram of a transcutaneous oxygen saturation concentration measuring device. FIG. 10A is a principle diagram of pulse oximetry.
FIG. 11 is an example of measurement data measured by pulse oximetry.
FIG. 12 is a diagram showing a principle of measuring a light absorption coefficient in a minute region.
[Explanation of symbols]
1. Variable frequency coherent light source
2 Optical scanning system
3 Detector
4 Amplifier
5 A / D converter
6 Data analysis system
7 samples
11 Partial reflection mirror
12 Reference mirror 12
13 Reference light
14 Measurement light

Claims (6)

A tissue having blood components is irradiated with light beams of two or more different wavelength regions, and in the region along the light beam, the intensity of the backscattered light of the irradiated light beam is reduced to a minute region of about 1 to 1000 microns in the light beam direction. Measuring separately; and
The absorption coefficient of light in the minute region is determined for each wavelength region from the intensity of the backscattered light from the minute region before and after the minute region in the light beam direction, measured for the light beams in the two or more different wavelength regions. Steps and
From the light absorption coefficient value in the minute region, utilizing the fact that the wavelength dependence of the light absorption coefficient differs between oxygenated hemoglobin and reduced hemoglobin, the amount of oxygenated hemoglobin, the amount of reduced hemoglobin, the amount of total hemoglobin, or the amount of oxygen in the minute region Determining at least one of the degrees of saturation;
A method for measuring oxygen saturation. Using light beams of two or more different wavelength regions, tomographic image data of a tissue having a blood component obtained separately for each wavelength region is analyzed, and a light beam of a specific minute region of the tissue having the blood component is analyzed. From the intensity of the backscattered light from the front and rear minute regions in the direction, the step of determining the light absorption coefficient in the minute region for each wavelength region,
From the light absorption coefficient value in the minute region, utilizing the fact that the wavelength dependence of the light absorption coefficient differs between oxygenated hemoglobin and reduced hemoglobin, the amount of oxygenated hemoglobin, the amount of reduced hemoglobin, the amount of total hemoglobin, or the amount of oxygen in the minute region Determining at least one of the degrees of saturation;
A method for measuring oxygen saturation. A tissue having blood components is irradiated with light beams of two or more different wavelength regions, and in the region along the light beam, the intensity of the backscattered light of the irradiated light beam is reduced to a minute region of about 1 to 1000 microns in the light beam direction. Backscattered light intensity measuring means for separately measuring;
The absorption coefficient of light in the minute region is measured from the intensity of backscattered light from the minute region before and after the minute region in the light beam direction, which is measured for light beams in two or more different wavelength regions by the reflected light intensity measuring means. Light absorption coefficient calculating means to be obtained for each wavelength region,
From the light absorption coefficient value in the micro area determined by the light absorption coefficient calculation means, utilizing that the wavelength dependence of the light absorption coefficient is different between oxygenated hemoglobin and reduced hemoglobin, the amount of oxygenated hemoglobin in the micro area, Oxygen saturation or the like calculating means for calculating at least one of reduced hemoglobin amount, total hemoglobin amount or oxygen saturation,
An oxygen saturation measuring device comprising: A tomographic image display means for displaying at least one of the oxygenated hemoglobin amount, the reduced hemoglobin amount, the total hemoglobin amount or the oxygen saturation determined by the oxygen saturation etc. calculating means as a tomographic image in the tissue having the blood component; The oxygen saturation measuring device according to claim 3, wherein: Light generation means having means for generating light having a coherent length longer than the length in the light beam direction of the sample to be measured, and means for continuously or discretely changing the wavelength thereof,
Two optical paths of a reference optical path and a sample optical path having different optical path lengths for guiding light from the light generating means,
Light combining means for combining light passing through the reference light path and light scattered from the sample placed in the sample light path,
Light intensity detecting means for detecting the intensity of the light multiplexed by the optical multiplexing means,
A signal analysis unit that analyzes the light intensity signal obtained by the light intensity detection unit and obtains a light absorption coefficient for each minute area on the light beam of the sample placed in the sample optical path;
3. The method for measuring oxygen saturation according to claim 1 or 2, wherein: Light generation means having means for generating light having a coherent length longer than the length in the light beam direction of the sample to be measured, and means for continuously or discretely changing the wavelength thereof,
Two optical paths of a reference optical path and a sample optical path having different optical path lengths for guiding light from the light generating means,
Light combining means for combining light passing through the reference light path and light scattered from the sample placed in the sample light path,
Light intensity detecting means for detecting the intensity of the light multiplexed by the optical multiplexing means,
A signal analysis unit that analyzes the light intensity signal obtained by the light intensity detection unit and obtains a light absorption coefficient for each minute area on the light beam of the sample placed in the sample optical path;
The oxygen saturation measuring device according to claim 3 or 4, wherein:

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