JPH04200535A - Optical measuring method and instrument - Google Patents

Abstract

PURPOSE:To measure the concn. of the materials constituting a living body by applying the principle that the ratios of respective materials can be measured from the velocities of the light, transmitted through the materials in the case of the distribution of the plural materials varying in refractive index on an optical path length, if the optical path length is known. CONSTITUTION:The light of a light source section 1 is used by opening only the shutter 3 and the time when the light of this wavelength transmitted through the living body is measured, by which the quantity proportional to the blood volume in a measuring region is obtd. The similar measurement is then made by opening only the shutter 4 and using a light source section 2 of the wavelength varying in the refractive index of oxygenated red cells and deoxygenated red cells to determine the time when the light of the wavelength from the light source section 2 transmits the living body. The quantity proportional to the oxygenated red cell and deoxygenated red cell quantities is thereby measured. A series of such measurements are carried out from all directions by rotating or linearly moving the living body 10 relative to the incident light. The tomographic image of the blood volume in the living body or the satd. degree of oxygen which is the ratio of the oxygenated red cells to the total red cell quantity is obtd. by an ordinary tomographic image reproduction technique using a computer 15.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method and apparatus for noninvasively measuring information inside an object, such as information inside a living body, using light.

[Conventional technology]

Recently, attempts have been made to detect lesions in living organisms by measuring and imaging abnormalities in metabolic functions in tissues or cells. One of the devices currently in use is PET (Positro
n Emission Tomography), but in this case, it is highly invasive because it is necessary to inject radioactive elements into the living body. Therefore, several optical CT apparatuses have been proposed that attempt to measure and image metabolic functions within a living body using visible to near-infrared light, which is non-invasive to the living body. For example, the device described in Japanese Patent Application Laid-open No. 63-206655 alternately irradiates a living body with near-infrared light of multiple wavelengths, and uses the device to reduce hemoglobin (Hb), which is involved in metabolic functions in the living body.
) concentration or oxygen saturation or cytochrome aa,
The oxidation state of these substances is detected as changes in the amount of light absorbed by these substances, and CT technology, which is known as computerized tomographic image reconstruction technology, is used to obtain tomographic images that represent metabolic functions within the body. It is.

[Problem to be solved by the invention] Since living organisms are basically composed of cells with a size of several μm to several tens of μm, when a living body is irradiated with visible to near-infrared light, most of the light is It is scattered by cells.

Therefore, the light that has passed through the living body includes both light that has passed through the shortest optical distance within the living body and light that has been multiple scattered and transmitted through the living body. Here, the positional information of light that has passed through the shortest optical distance within a living body can be approximately considered to lie on a straight line connecting the site where the light entered and the site where it was detected, but Since light travels in a zigzag pattern throughout a living body, its positional information is not clear. Therefore, it is difficult to obtain a tomographic image with high spatial resolution using detection light in which these lights are mixed. Therefore, in order to obtain accurate position information, it is necessary to separate the light that has passed the shortest distance from the multiple scattered light. In the above-mentioned Japanese Patent Application Laid-Open No. 63-206655, a sample light pulse in which ultrashort pulse light irradiated into a living body is temporally spread due to multiple scattering, and a reference light pulse delayed by an arbitrary amount of time outside the living body are combined into a nonlinear method. By introducing the light into an optical crystal and detecting the resulting second harmonic, the light that has passed through the shortest optical distance within the body is separated. However, in order to obtain information regarding metabolism in the living body from this separated light, it is necessary to distinguish between the weak part of the transmitted light based on the scattering characteristics of the living body and the weak part of the transmitted light based on the light absorption of Hb or cytochrome aa. It is necessary to further separate the two, but this is not considered in the above-mentioned known example.

[Means for Solving the Problems] The cause of the above-mentioned problems is deeply related to the principle that metabolic functions in a living body are measured by measuring the intensity of light transmitted through the living body. That is, Hb, cytochrome a
Is the amount of light absorption such as a, etc. measured as an attenuation of the transmitted light intensity?In addition to the light absorption by these substances, the scattering characteristics of the living body are included as factors involved in the attenuation of the transmitted light intensity. There is. Therefore, the present invention utilizes the measurement of the light transmission rate of red blood cells containing (b) in order to obtain the blood volume or the oxygen saturation of Hb in a living body as a measurement quantity that is separated from the light scattering phenomenon caused by living tissues. Methods and apparatus are provided.

[Effect 1 The transmission speed of light in a substance depends on the refractive index of that substance. Therefore, if the optical path length is known, if a plurality of substances with different refractive indexes are distributed along the optical path length, the ratio of each substance can be measured from the speed of the transmitted light. By applying this principle to living organisms, the concentration of substances constituting the body can be measured. For example, biological tissues such as blood, lung tissue, and fat have unique refractive indexes that differ from each other.
n) and L.E. Preus
s) and R.C.Tay
, or) and R. Shei Feresis (R,J,
``Refractive index of mammalian tissue using fiber optic cladding method''
ve 1ndex of some mammalia
tissues using a fiber o
ptic cladding method) J, 19
June 15, 1989, Applie Optics, Volume 28, No. 12, Paragraphs 2297-2303 (Appliec
l optics, 28.12.2297 (1989
)). According to their results, blood,
lung tissue.

The refractive index of fat is 1, 40, 1.38° and 1.4, respectively.
6. Therefore, for example, the amount of blood in a living body's head can be measured by measuring the time that light passes through the head using the refractive index of brain tissue and the refractive index of blood.

Furthermore, the refractive index of red blood cells containing Hb is
Deoxygenation differs depending on the deoxygenation state, as described in ``The determination of oxygen availability in the microcirculation'' by Pittman, R.N. and Duling, B.R.
nation of oxygen available
ity in the microcirculati
on),” published by Professional Information Library, 1977.

Oxygen & Physiol, edited by F.F.
logical function)J.

Paragraphs 133-147, and J6M Steinke and A.P. Hepherd [Role of Light Scattering in Whole Blood Oximetrini]
light scattering in whole
blood oximetry) J, March 1986.

iTripleE Transactions of Biomedical Engineering, BME-Volume 33,
No. 3, paragraphs 294-301 (IEEE Trans,
Biomed, Eng., BME-33,3,29
4 (1986)). H.M. Steinke et al. calculated the increase in absorbance with respect to changes in red blood cell concentration using the Twersky Equa
tion) to determine the value of the constant related to light scattering by red blood cells. Since this constant is expressed as a function of the refractive index of red blood cells, calculating the value of the refractive index gives us
If the refractive index of oxygenated red blood cells, in which Hb in red blood cells is oxygenated, is 1.40, then at a wavelength of 813 nm, the refractive index of deoxygenated red blood cells, in which Hb in red blood cells is deoxygenated, is It becomes 1.39. Moreover, such a difference in refractive index hardly occurs between 660 nm and 940 nm. Generally, the wavelength change in the refractive index of a substance becomes remarkable near the absorption band, and in the case of Hb, the oxygenated and deoxygenated states of Hb exhibit characteristic absorption spectra at wavelengths from visible to infrared light. Therefore, in this wavelength range, differences in refractive index occur depending on the oxygenation state of red blood cells. Therefore, by detecting the difference in light transmission rate caused by the difference in refractive index depending on the oxygenation state of red blood cells, it becomes possible to determine the concentration ratio of oxygenated red blood cells and deoxygenated red blood cells in the body. The advantage of this method is that the measured quantity is the light transmission rate, so when the ultrashort pulse light irradiated to the living body passes through the living body and is detected by a highly sensitive time-resolved photodetector such as a streak camera, the detection level will be reduced. If a timetable that is recognized to have exceeded the ground level is detected, that timetable itself contains information about the oxygen metabolism function in the living body, and at the same time, it has passed through the shortest optical distance within the living body. . Therefore, by using the present invention, tomographic images of in-vivo metabolic functions can be measured with good spatial resolution and contrast.

[Embodiment] FIG. 1 is one of the embodiments of the present invention, and is a diagram showing the configuration of the entire apparatus. Light source section with different wavelengths
and the light source section 2, for example, each have a pulse width number p s
e c, the following ultra-short pulse light is emitted, and the light is sent to the shutter 3. lenses 5 through shutters 4, respectively. The lens 6 turns the light into parallel light. Here, the wavelength of the light source section 1 is set to 940 nm, which has the same refractive index of oxygenated red blood cells and deoxygenated red blood cells.
Furthermore, the wavelength of the light source section 2 may be set to 813 nm, where the refractive index of oxygenated red blood cells is larger than that of deoxygenated red blood cells.

The light made parallel by the lens 5 is introduced into the half mirror 9 via the mirror 7 and the half mirror 8, and the light made parallel by the lens 6 is introduced into the half mirror 9 via the half mirror 8. This half mirror 9 separates the living body light that irradiates the living body 1o and the reference light that passes outside the living body. The separated light as living body light passes through the living body 10 and passes through the mirror 11.
．． The light is detected by the time-resolved light detection section 13 via the half mirror 12. As this time-resolved light detection section 13, for example, a streak camera may be used. Further, the light separated as a reference light by the half mirror 9 is transmitted to the mirror 14.
The light is detected by the time-resolved light detection section 13 via the half mirror 12. Here, the in-vivo transmission time t of light can be determined, for example, as follows. Of the biological light and reference light separated by the half mirror 9, the reference light that has passed through the air is sent to the time-resolved light detection section 13 according to the time schedule shown in FIG. is detected as pulsed light. Here, in FIG. 2, the horizontal axis represents the timetable of detected light, and the vertical axis represents the intensity of light.

On the other hand, the biological light transmitted through the living body 1o is detected by the time-resolved light detection unit 13 with a slight delay from the reference light due to the difference in refractive index between the living body and the air, and is further detected by the time-resolved light detection unit 13 due to multiple scattering of light within the living body. However, the light that has passed through the shortest optical distance within the living body is detected at the time schedule t1 in FIG. 2.

Here, the optical shortest distance d within the living body may be approximately expressed as a straight line distance connecting the light incident position and the light exit position into the living body. Then, the in-vivo penetration time t of light is expressed by the following equation using the speed of light ring C in vacuum.

1=1. -1°-cD The third term on the right side of this equation is a correction term for making the optical path lengths of the reference light and the living body light the same except for the living body passing distance.

Now, measurements for obtaining a tomographic image of metabolic function using a value of 20°C are performed, for example, as follows. First, shutter 3
Using the light from the open light source section 1, the living body penetration time 11.1 of the light of that wavelength is measured. Since the refractive index n*EDa+ of red blood cells at this wavelength is constant regardless of oxygenation or deoxygenation of red blood cells, can be expressed as follows.

t-+ = P TxaD/ (c/ nt++s6.
) + P *toD/ (c/n REDa+)
Here, P TI & + P RED respectively represent the concentration ratio of living tissue and blood in the light transmission region, and C represents the speed of light ring in vacuum. Here, P TXa= I Pa
If go, then C1. By measuring , an amount of PIItDD proportional to the blood volume in the measurement area can be obtained. Next, with only the shutter 4 open, a similar measurement is performed using the light source section 2 whose refractive index is different for oxygenated red blood cells and deoxygenated red blood cells, and the living body penetration time for the wavelength of the light source section 2 is calculated.
Find 1.

L a+ :P *ioD/(c/nTIaaj+
Pago---y D/('C/ n *tr
s'---y-r)+P RED-a **++y
D / (C/ n*to-* tamyar) Here, nTIam++ nRED-s*yat+ nR
ED-de*++yal is the living tissue corresponding to the wavelength of the light source section 2, respectively.

Represents the refractive index of oxygenated red blood cells and deoxygenated red blood cells.

Also P□. -allF*PREゎ-mee++7 represents the concentration ratio of oxygenated red blood cells and deoxygenated red blood cells in the light transmission region, respectively, and P□ゎ-19,□'' P RED
From the relational expression P *tゎ-ezy, by measuring f, PRID-amF D + P**o-m, which is an amount proportional to the amount of oxygenated red blood cells and deoxygenated red blood cells, is obtained.
t*xyD can be measured.

This series of measurements is performed from all directions by rotating or linearly moving the living body 10 with respect to the incident light, and the blood volume in the living body or the total red blood cell volume is determined using normal tomographic image reproduction technology using the computer 15. A tomographic image of the oxygen saturation, which is the ratio of oxygenated red blood cells to the oxygenated red blood cells, is obtained and displayed on the display section]6. Here, the opening and closing of the shutter 3 or the shutter 4 and the movement or rotation of the irradiated object 10 are controlled by the computer 15.

Furthermore, the present invention can also be used to obtain tomographic images of specific tissues within a living body, such as lung tissue or liver, by taking advantage of the fact that each living tissue has a unique refractive index. . Furthermore, the present invention can be used not only for measuring the damage of living bodies but also for objects having internal refractive index distribution.

[Effects of the Invention] According to the present invention, it has become possible to measure tomographic images of in-vivo metabolic functions with good positional accuracy and contrast.

[Brief explanation of the drawing]

FIG. 1 is a configuration diagram of an optical measurement device showing an embodiment of the present invention;
FIG. 2 is a reference diagram for determining the rate of light penetration through a living body. 1.2... Light source section, 3, 4... Shutter, 5, 6
... Lens, 7, 11.14 ... Mirror, 8, 9.1
2... Half mirror 110... Living body, 13... Time resolved light vz diagram

Claims (1)

[Claims] 1. Light characterized by measuring the concentration of the constituent substances of the object by irradiating an object made of a plurality of substances with pulsed light from the outside and measuring the speed at which the light passes through the object. Measurement method. 2. Pulse light is irradiated to a specific part of a living body that contains substances with different light transmission rates depending on the degree of metabolic function, and the rise time of the emission of transmitted light from the living body is measured. An optical measurement method characterized by measuring metabolic function by measuring transmission rate. 3. The optical measurement method according to claim 2, wherein the metabolic function is measured by measuring the light transmission rate of red blood cells contained in the living body. 4. A light source unit that emits pulsed light with a wavelength in the visible to infrared region, a light irradiation unit that irradiates an object with light from the light source unit, and a light time intensity detection unit that detects the intensity of light transmitted through an object over time. What is claimed is: 1. An optical measuring device comprising: a display section that displays a detected signal; 5. The optical measuring device according to claim 4, further comprising: a light branching section that branches the light from the light source section into a section that irradiates the object and a section that passes through the outside of the object; An optical measurement device comprising a light merging section that recombines the light that has been used. 6. The optical measurement device according to claim 5, wherein a plurality of light sources having different wavelengths are used in the light source section. 7. The optical measuring device according to claim 6, including a moving and rotating unit that moves or rotates the object relative to the incident light, and a computer that performs signal processing of the transmitted light of the light that is incident on the object from all directions. Characteristic optical measurement device.