JPH0620458B2 - High directivity imaging element and high directivity imaging device - Google Patents

Description

TECHNICAL FIELD The present invention relates to a highly directional imaging element and a highly directional imaging apparatus suitable for detecting an absorption distribution in a scattering body such as a living body.

[Conventional technology]

Since the discovery of X-rays, a technique (non-invasive or non-invasive measurement method) for observing the inside of a living body (human body) from the outside without any damage has been strongly demanded and developed in the field of biology, particularly in medicine. It was This technology uses gamma rays and X-rays having the shortest wavelengths when viewed as electromagnetic waves, and radio waves having the longest wavelength. The former is X-ray CT and the latter is NMR-CT.
(Magnetic Resonance Image
ng, MRI).

On the other hand, the spectroscopy of ultraviolet-visible-near-infrared-infrared region, which is widely used in the fields of physics and chemistry, is called "whole body" (i.
There are relatively few attempts to apply it to (n vivo). This is because many problems regarding the most basic "quantitativeness" remain unsolved in the main measurement using light, especially those utilizing the processes of absorption and light emission. Current,
A reflection spectrum measuring device using a solid-state element and a high sensitivity T
Although measurement with a V camera or the like has been attempted, it is for this reason that the reproducibility and the reliability of the obtained absolute value are low.

When light is emitted from a scatterer such as a biological tissue, straight light can be extracted to some extent by receiving light 180 degrees facing each other, but at present, its spatial resolution is not very good.

The difference in spatial separation between X-rays and light cannot be filled up so far. However, the use of light, especially near infrared light, should allow imaging of tissue oxygen concentration from hemoglobin in blood. These will give different information from other NMR-CT and X-ray CT.

With a tissue thickness of 3-5 cm, we can detect the transmitted light. This means that "light-radiography" can be used for diagnosis. Female breasts have relatively uniform tissue and light is easily transmitted, and the transmitted light can be easily detected (thickness: about 3 cm) from its shape,
Diaphanograph has been used to diagnose breast cancer since ancient times.
It has been used under the name y (Light scanning). Such a conventional diagnostic device will be described with reference to FIG.

FIG. 38 is a diagram showing the configuration of a conventional device for obtaining a light absorption distribution image. In the figure, 401 is a scan head, 403 is a human body, 405 is a video camera, 407 is an A / D converter, 409 is a near infrared light frame memory, 411 is a red light frame memory, 413 is a processor, 415 is a color conversion processing unit. Reference numeral 417 is an encoder keyboard, 419 is a D / A converter, 421 is a printer, 423 is a television monitor, and 425 is a video tape recorder.

Red light (mainly strongly absorbed by hemoglobin in blood) and near-infrared light (absorbed by blood, water, fat, etc.) are alternately passed through the light guide by the scan head 401 to a measurement site of the human body, for example, Scan while illuminating the breast.
In the figure, light is emitted from the bottom to the top. As a result, the whole breast shines brightly, this transmission image is captured by the video camera 405, converted into a digital signal by the A / D converter 407, and near-infrared light and red light are respectively stored in the frame memories 409 and 411 via the digital switch. The processor 413 calculates the intensity ratio of near-infrared light and red light from the data in both frame memories, and further performs color conversion processing to convert into an analog signal.
Observe the light absorption distribution image on a video tape.

In this device, the light from the scan head 401 is not parallel light, and the light is spread by the tissue (breast) as if it was illuminated by a flashlight, and this is received by a two-dimensional detector such as a video camera. The resolution is not very good.

An example in which this point is improved and a collimated irradiation-light reception system is used will be described with reference to FIG.

FIG. 39 is a diagram showing the configuration of a conventional device for obtaining a light absorption distribution image using a collimated irradiation-light receiving system.

In this example, a laser beam is used as a light source, a laser is guided by an optical fiber 433 to irradiate a measurement target 435, and the transmitted light is captured by a fiber collimator 437 and detected by a detector 4
The signal is converted into an electric signal by 43, and the signal is processed by the computer 451 through the preprocessing circuit 445, the A / D converter 447, and the interface 449. In this case, the irradiation optical fiber 433 and the fiber collimator 437 for detection are synchronously scanned by the motor 439 to obtain a light absorption distribution image of each site of the measurement target and observe it on the monitor 453.

As a light source, a He-Ne laser of 633 nm is used as red light, and a semiconductor laser of 830 nm is used as near-infrared light. In 1977, Jobsis et al. Succeeded in detecting the light transmitted by irradiating the heads of cats and humans with near-infrared light, and reported that the amount of transmitted light fluctuates depending on the respiratory condition of the animal. Near-infrared light with a wavelength of 700 to 1500 nm can detect sufficiently transmitted light with an irradiation light amount of about 5 mW if the tissue is about the size of a cat's head. This light amount is about 1 of the current laser safety standards. / 50 or less. Also, it is about 1/10 of the near infrared light that we see on the coast, which is very safe.

[Problems to be solved by the invention]

By the way, when a living body is irradiated, the transmitted light is absorbed and scattered by the sample.

FIG. 40 is a diagram showing a Twersky's theory of scattering, in which the relationship between the absorbance of erythrocyte suspension and the hematocrypt concentration was determined, and the transmitted light intensity and transmitted light obtained when laser light with a wavelength of 940 nm was irradiated. 2 shows the scattering component and the absorbance component of.

As can be seen from FIG. 40, the transmitted light has a large scattering component superimposed on the absorbance component. Since the scattered component has no directivity, scattered light from various parts is included, which has the property of making the optical tomographic image blurred. Therefore, even if the transmitted light is simply detected, the absorbance component of the information necessary for the scattered component cannot be detected accurately.

By the way, in a conventional device as shown in FIGS. 38 and 39, transmitted light is detected by any of the methods shown in FIGS. 41 (a) to (c), 42 (a) and (b). is doing.

FIG. 41 (a) shows a system in which a sample 460 is irradiated with a fine-bundle beam and transmitted light is detected by a detector 464 through a screen 462 having a predetermined aperture diameter. However, since the fine-bundle beam is scattered by the sample and a light-receiving directional light beam determined by the front aperture diameter is detected by the detector,
Light other than the straight light flux, that is, a scattered component will also be detected depending on the degree of spread of the fine bundle beam.

FIG. 41 (b) shows a method in which a thick bundle plane wave is applied to the sample 460 and transmitted light is detected by a detector 464 through a screen 462 having a predetermined aperture diameter. In this case as well, the light flux within the light receiving directivity determined by the aperture diameter is similarly detected,
Scattered light other than the light flux that travels straight will also be detected.

In FIG. 41 (c), a lens 466 is arranged behind the sample 460 to form an image, which is detected by the detector 464. The divergent spherical wave emitted from each point of the sample is imaged by the lens. Since it is detected as a focused spherical wave that forms an image at, not only the straight component of the light beam but also the light receiving directional light beam that is determined by the lens aperture and focal length is detected, and similarly, all the scattered components are picked up. , The resolution is extremely poor.

FIG. 42 shows a method of detecting transmitted light with a fiber collimator. The figure (a) shows a method in which the refractive index of the core and the clad is changed stepwise, and the figure (b) shows the distribution of the refractive index of the cocoa. It is a method that has. In either case, since the fiber collimator receives light in a certain solid angle range, it receives light other than the straight-ahead component, that is, scattered light, resulting in extremely poor resolution. .

The present invention is for solving the above-mentioned problems, and even when many scattered components are contained in transmitted light, the scattered components can be surely removed, and only necessary information on the absorbing component can be extracted. An object of the present invention is to provide a high directivity image forming device and a high directivity image forming apparatus.

[Means for Solving the Problems]

In the present invention, a light absorbing material is applied to the inner wall surface, or a linear hollow thin tube in which the refractive index of the core portion is smaller than the refractive index of the cladding portion, or a bundle of these, or an absorbent material is applied to the wall surface. A highly directional imaging system is used in which two sets of the above-mentioned plurality of plates are arranged so as to intersect each other. Utilizing the fact that the laser light is a coherent light wave and has a sharp directivity, the laser light is applied to the measurement target and the transmitted light is received by the highly directional imaging system. The input wave becomes a plane wave due to Fraunhofer diffraction, and only the rectilinear component is detected, and the components other than the rectilinear component are attenuated. That is, when non-directional light such as incoherent light and scattered light is received by a highly directional imaging system, the attenuation is large and the re-emitted light from the imaging system is not strong enough to be used by the laser. Coherent light such as light can be extracted as strong re-emitted light without much attenuation. Therefore, the present invention has a function of separating coherent light from incoherent light. By using such a highly directional imaging system, by irradiating an object including a scatterer such as a human body with a laser beam and detecting the transmitted light, the influence of the scattered component is removed and a high resolution is obtained. It becomes possible to observe an optical tomographic image.

[Action]

The present invention uses a laser light as an irradiation light source, and when detecting transmitted light containing a lot of scattered components such as a living body to obtain an optical tomographic image, only the straight-ahead component parallel to the optical axis of the transmitted light is extracted A component that is not parallel to the optical axis is attenuated to reliably remove the scattered component, and only the optical absorption information can be extracted, so it is possible to observe an optical tomographic image of a living body or the like with extremely high resolution. .

〔Example〕

 Hereinafter, embodiments will be described with reference to the drawings.

FIG. 1 is a diagram showing a plane-wave highly directional imaging element used in the optical tomographic imaging apparatus of the present invention. In the figure, 100 is a highly directional optical element, 103 is a light absorbing material, 105 is a core, 10
7 is a clad.

In FIG. 1 (a), the highly directional imaging element 100 is made of, for example, a linear elongated hollow glass fiber, and a light absorbing material such as carbon is applied to the inner wall surface thereof.

If light is incident from the incident surface 105, the optical element 10
Light parallel to the optical axis of 0 goes straight out and is emitted from the emission surface 107, but light having an inclination with respect to the optical axis hits the wall surface and is absorbed by the absorber 103 and does not appear on the emission surface side. Here, when the aperture diameter of the high directional imaging element 103 is D, the length is 1, and the wavelength of the incident light is λ, a component that is not parallel to the optical axis is absorbed, and a flank completely generated by a plane wave is emitted on the exit surface side. As a Forfar diffraction image, it becomes a substantially point light source, and by detecting it, only the plane wave is detected as a length l
Has a relationship of l∝D ² / λ. That is, this is the distance at which the Franforfer diffraction image can be observed.

For example, when λ = 6328Å, when D = 10 mm, l =
600 m, l = 6 m when D = 1 mm, l = 6 cm when D = 0.1 mm, l = 0.6 mm when D = 0.01 mm, D =
L = 6 μm when 1 μm, l = when D = 0.5 μm
It is 1.25 μm.

Therefore, set the aperture diameter and length appropriately according to the measurement target,
If the imaging element is made sufficiently longer than the entrance aperture diameter, only the plane wave parallel to the optical axis can be extracted from the exit surface of the light incident on the highly directional imaging element. However, it is necessary that the tube diameter is large as compared with the wavelength of the incident light so that substantially plane wave propagation can be performed. If the diameter is about the same as the wavelength of the incident light, the diffraction is large and the amount of light that can be extracted from the exit surface is extremely small.

In FIG. 1 (b), the refractive index of the core 109 is made smaller than the refractive index of the cladding 111, contrary to the ordinary optical fiber. Light that is not parallel to the optical axis is dissipated without being totally reflected by the cladding 111, Even if it is partially reflected, all the light that is not the optical axis is lost to the outside of the optical element after repeating the reflection several times, and eventually only the plane parallel to the optical axis can be extracted from the emission surface 107. The light absorbing material may be applied to the inner surface of the clad by combining FIGS. 1 (a) and 1 (b).

FIG. 2 is a view showing an embodiment in which the high directivity image forming elements shown in FIG. 1 are bundled in a cylindrical shape. In the figure, 120 is a high directivity imaging system, and 121 is a radiation directivity pattern. This radiative directivity is determined by the incident light wavelength λ and the tube diameter D, and the smaller the tube diameter, the closer to spherical wave radiation.

As shown in the figure, when the high directivity imaging elements 100 are bundled in a cylindrical shape to form the high directivity imaging system 120, the outgoing light indicated by the radiation directivity pattern 121 is obtained from each high directivity imaging element. Therefore, when the light including the scattered light and the plane wave is incident on the incident side, it becomes a substantially point light source as a Franforfer diffraction image by the plane wave from the exit surface 107, and by detecting it, only the plane wave is detected. It is possible. Therefore, if the light receiving surface of the highly directional imaging system 120 is made to have a predetermined size, the transmitted light of the human body or the like can be detected at a time within a predetermined range, and a high light tomographic image can be obtained. It can be used as a resolution detector.

FIG. 3 is a diagram showing an example in which a convex lens is provided on the incident surface side of the highly directional imaging system shown in FIG. In the figure, 123 is a convex lens and 125 is a pinhole.

FIG. 3 (a) is a diagram showing an example in which a convex lens 123 is provided on the incident surface. In this embodiment, a convex lens 123 is used to form a Franforfer diffraction image on the focal plane, and the plane wave incident light is converged to form a paraxial line. Other than light rays are absorbed by the inner surface of the optical element 100, and only the straight light component parallel to the optical axis can be detected. In this case, the length of the highly directional imaging element becomes the focal length of the lens and the light is extracted through the pinhole.

Further, as shown in FIG. 3 (b), a pinhole 125 may be provided at the focal position of the convex lens 123 to lengthen the highly directional imaging element. In this case, the position of the pinhole 125 is the focal position when the focal length of the convex lens is f, and the position of the detector may be farther than f with respect to the lens.
If the distance is more than 2f, the loss in the wall of the highly directional optical element increases, so it is desirable to set it in the range of f to 2f.

FIG. 4 shows an optical fiber 127 on the incident surface side of the highly directional imaging system.
In the figure showing an example in which the refractive index of the optical fiber is larger than that of the clad portion in the optical fiber, the optical fiber plays the same role as the convex lens in FIG. 3 and can improve the directivity. . On the contrary, by providing an optical fiber on the exit surface side of the highly directional imaging system, it is possible to handle the image flexibly.

The structure shown in FIGS. 2 to 4 is formed as a high resolution optical system by forming a multi-channel type as shown in FIG. 5 by applying a thin film manufacturing technique or the like. Good.

Next, the spherical wave height directivity imaging system of the present invention will be described with reference to FIGS.

FIG. 6 is a diagram showing a basic configuration of a spherical wave high directivity imaging system, which is configured by conically bundling radially so that the optical axis of each high directivity imaging element diverges from one point. It is a thing.

In the present embodiment, incident light that is not parallel to the optical axis of each highly directional imaging element 100 is attenuated, and only spherical waves traveling parallel to the optical axis can be extracted from the exit surface.

FIG. 7 shows a structure in which a convex lens 123 is provided on the incident surface side of the optical system of FIG. 6, and the convex lens has the same function as in the case of FIG. 3 and can further improve the high directivity. Of course, also in the example of FIG. 7, pinholes may be provided to further improve the directivity, as described in FIG. 3 (b).

FIG. 8 shows an optical fiber 127 provided on the incident surface side.
The optical fiber has a function similar to that of a convex lens and can improve directivity. The opposite is also possible.

FIG. 9 is a view showing how to bundle the high-directivity image forming elements of FIGS. 6 to 8. Each optical element is bundled so as to have an optical axis radially radiating from the same point, so that a spherical wave A highly directional imaging system can be constructed. In this case, each high-directivity imaging element 100 is a thin tube having a small diameter at one end and a large diameter at the other end so that the diameter becomes continuously thicker from the incident surface side to the exit surface side. It is possible to configure a spherical wave height directivity imaging system that transmits only spherical waves radiated from the.

FIG. 10 shows an example in which the high-directivity imaging element has a rectangular cross section, and a hole is formed in one by bundling the high-directivity imaging elements 101 having a rectangular cross section or using a plurality of plates. The optical system having a high directivity can be configured similarly to the case of the cylindrical optical system.

FIG. 11 is a diagram showing an example in which a high directional imaging system similar to that in FIG. 10 is configured by two sets of optical plate groups 150 and 151 which are separately arranged so as to be orthogonal to each other. In the present embodiment, first, the high directivity optical plate 150 attenuates light whose traveling direction is perpendicular to the optical axis, and then the high directivity optical plate 151
Rays whose traveling direction is horizontal and have an angle with the optical axis are attenuated, and as a result, only rays parallel to the two sets of plates can be extracted from the exit surface side.

FIG. 12 (a) is a diagram showing a spherical wave height directivity imaging system having a rectangular cross-sectional spherical area, which is formed by bundling a plurality of optical elements whose rectangular cross-sectional areas are continuously large or by vertically directing high directivity. The optical optics plate group and the high directivity optics plate group intersecting with the optical optics plate group are radially arranged so as to have an optical axis diverging from one point.

Further, FIG. 12 (b) shows two sets of highly directional optical plate groups 16 which are radially separated and arranged so as to diverge at a predetermined angle.
1 shows a highly directional imaging system composed of
As in the case of FIG. 1, each plate group 161, 162 attenuates all but the spherical wave propagating in the optical axis direction, and only a predetermined spherical wave can be extracted.

FIG. 13 is a diagram for explaining a laser irradiation method for a sample in the present invention, in which 170 is a sample, 171 is a beam contractor, 173 is a scanning device, 175 is a beam expander, and 177 is a convex lens.

In FIG. 13 (a), the beam is reduced by the beam reducer 171, and the sample 170 is irradiated while being scanned in the X-axis and Y-axis directions by the scanning device 173. The transmitted light of the sample 170 consists of light carrying information of absorption by the sample and light scattered by the sample. The transmitted light is detected by the highly directional optical system of the present invention to attenuate the scattered light. Only light bearing absorption information can be detected.

In FIG. 13B, the laser beam is expanded by the beam expander 175.
By irradiating the sample 170 with the expanded plane wave, it is possible to detect without requiring a scanning mechanism.

In FIG. 13 (c), a spherical wave is obtained from the laser light by the convex lens 177, and this is irradiated onto the sample 170. In this case, by using the spherical wave high directivity imaging system of the present invention, Only light bearing absorption information can be detected.

FIG. 14 is a diagram showing an example of detecting sample-transmitted light using the highly directional imaging system of the present invention.

FIG. 14 (a) shows the case of detecting only the straight-ahead light transmitted from the sample, which uses the highly directional imaging system 100 and uses the detector 180 to determine the light flux determined by the diameter and length of each optical element. Only travels through the optical element and detects this. In this case, the directivity can be further increased by increasing the length of the tube.

FIG. 14 (b) is a diagram showing a case where the transmitted light of the spherical wave is detected, in which the spherical wave high directivity imaging system 130 is used and the detector 18
By detecting 0, only spherical waves diverging at a predetermined angle can be detected.

FIG. 14 (c) is a diagram showing another embodiment of the present invention using a telescope. In the figure, 182 is a telescope and 184 is a lens. In the present embodiment, when a lens 184 having a focal length f of the telescope 182 which is much larger than that of a camera lens is used and its aperture diameter is D, the viewing angle is determined by D / f and becomes very small. Therefore, by irradiating the sample with light and arranging it at a distance l sufficiently far from it, where l is a distance l> f, the light flux entering the detector can obtain only a straight-ahead component within the viewing angle range. However, in the present embodiment, it is difficult to bundle a plurality of telescopes in a sufficiently dense manner, and since it is not a perfect Franforfer image, there is a problem that some blurring occurs, but a sharp image can be obtained.

FIG. 14 (d) is a conceptual diagram of the detection method of the present invention. In the figure,
181 is a laser light source, 170a is an absorber, 170b, 1
70c is a scatterer and 186 is a lens.

As shown in the figure, the measurement target such as a living body is a scatterer 170b,
170c and the absorber 170a coexist, and by irradiating this with a laser light source and detecting using the highly directional imaging system of the present invention, the scattering component by the scatterer is removed and Only absorbing components can be detected.

The detection by the highly directional imaging system of the present invention is shown in FIG.
As shown in (a), when the light is directly detected by the detector 180, since the light obtained from each optical element is separated, the image is observed as a group of discontinuous points. Light may interfere with each other to generate unnecessary interference fringes. Therefore, as shown in FIG. 15 (b), by inserting a ground glass 183 between the highly directional imaging system and the detector 180, the image observed as a discontinuous collection of light is smoothed and a beautiful image is obtained. In addition, the interference of the output light of each optical element can be eliminated to prevent interference fringes.

The output light from the highly directional imaging system may be detected by scanning the point detector 185 in the X-axis and Y-axis directions as shown in FIG. 16 (a). As shown in (b), it may be detected by scanning the one-dimensional array detector 187 in one direction, that is, in the Y direction in the figure.
Alternatively, the two-dimensional detector 189 may be used to detect at once.

In the present invention, laser light such as a continuous dye laser, a pattern dye laser, a YAG laser, and a semiconductor laser can be used, and the detector can be a photodiode capable of detecting a visible region or a near infrared region, a photo diode. A semiconductor detector such as a diode array, a MOS array, a CCD sensor, a photo-emission type pidicon, an image olicon, or the like can be used. As a detector with a multiplication function, a dynode or balunche photodiode combined with secondary electron detection is used, a secondary electron multiplication is performed with a microchannel plate, and the fluorescent image on the fluorescent surface is diode array, vidicon. , Those detected by image orthicon, etc. can be appropriately used.

FIG. 17 is a diagram showing the overall configuration of the optical tomographic imaging apparatus of the present invention. In the figure, 201 and 203 are lasers, 205 is a sector, 207 is a laser irradiation system, 209 is a sample, 211 is a detector, and 211a. Is a highly directional imaging system, 211b is a detector,
211c is a synchronous detector, 213 is a data processing unit, 213
a is an absorbent fabric calculation unit, 213b is a three-dimensional distribution calculation unit, 2
Reference numeral 15 is a sample table controller, and 217 is a sample table driver.

In the figure, the lasers 201, 203 are indicated by sector 205.
The laser light of the wavelengths λ ₁ and λ ₂ is alternately irradiated by the laser irradiation system 20.
The sample 209 is irradiated through 7. The transmitted light from the sample 209 is detected by the detector 211b through the highly directional imaging system 211a of the present invention. The detection signal is the sector 205.
The synchronous detection is carried out by the drive signal of, and the data processing unit 213 measures the absorption distribution. At the same time, the data processing unit 213 causes the sample table controller 215 and the sample table driving unit 217 to pass the sample 2
By rotating or moving 09, the transmitted light absorbed in each part of the sample is detected to detect the data processing unit 2.
A three-dimensional distribution image of absorption can be obtained from 13 to obtain an optical tomographic image. It should be noted that the transmitted light from the sample generally has a mixture of a scattering component and an absorbing component.

FIG. 18 shows an example of the absorbance characteristics with respect to wavelengths of oxygenated myoglobin and deoxygenated myoglobin. The scattering component has a small wavelength dependence and has a wavelength region in which it has a substantially constant value. Therefore, it is possible to remove the scattering component by using wavelengths λ ₁ and λ ₂ where the scattering component is almost constant and subtracting the respective absorbances. However, in the present invention, this scattered component can be completely removed by the highly directional imaging system.
By adopting the wavelength method, the absolute amount of absorption can be calculated.

In general, spectroscopic measurements on biological tissues are essentially inhomogeneous systems containing scattering particles. In this case, the Beer-Lambert law, which holds for a transparent sample, does not always hold. As a measuring method for such a cloudy sample, 2
There are wavelength and difference spectrum methods. Be at low sample concentration
Considering the case where the er-Lambert rule holds,
As shown in the figure (a), when the irradiation light amount is I ₀ and the transmitted light amount is I, log I ₀ / I = εcd (1) where epsilon is the extinction coefficient, c is the concentration, and d is the optical path length.

Similarly, for two different wavelengths λ ₁ λ ₂ , logI ₀ (λ ₁ ) / I (λ ₁ ) = ε (λ ₁ ) cd (2) logI ₀ (λ ₂ ) / I (λ ₂ ) = ε (λ ₂ ) cd becomes (3). From equations (2) and (3), log (λ ₂ ) / I (λ ₁ ) −log I ₀ (λ ₂ ) / I ₀ (λ ₁ ) = ε (λ ₁ ) −ε
(Λ ₂ ) cd (4) That is, the difference in absorbance between the two wavelengths is proportional to the concentration. Further, in the suspension sample, as shown in FIG. 19 (b), when I ₀ is the incident light, scattering and reflection component I _s are generated outside the transmitted light. Therefore, log I ₀ / I = εcd + I _s (5) Here, I _s represents attenuation due to scattering. Therefore, similarly, loI (λ ₂ ) / I (λ ₁ ) = ε (λ ₁ ) −ε (λ ₂ cd−logI ₀ (λ ₂ ) / I ₀ (λ ₁ ) + (I _s (λ ₁ ) − I ₂ ))… (6).

Therefore, if I _s (λ ₁ ) is equal to I _s (λ ₂ ), it is possible to measure the concentration of the sample by determining the difference in absorbance by removing the influence of scattering, and to make λ ₁ and λ ₂ close to each other. And let
Since it can be assumed that the effects of scattering etc. are almost equal,
The concentration of the sample can be determined from the difference in absorbance.

FIG. 20 is a diagram for explaining automatic gain control in the dual wavelength detection system. In the figure, 205 is a sector, 220 is a motor, 222 is a synchronization signal generator, 224 is a detection system, 2
Reference numeral 26 is an amplifier, 228 is a synchronous detection circuit, 230 is a feedback circuit, 232 is an amplifier, and 234 is a signal processing device.

In the figure, the motor 220 rotates the sector 205 more, and the detection system 224 alternately inputs the reference signal R and the detection signal S to the extraction amplifier 226. On the other hand, a signal synchronized with the rotation of the motor 220 is supplied to the synchronization signal generator 2
22 and an amplifier 226 is generated by this synchronizing signal.
Output is synchronously detected, and detection signal S and reference signal R
And separate. The separated reference signal R is negatively fed back to the input of the amplifier 226 through the feedback circuit 230 to adjust the gain.

In this way, the signal S is extracted in the state where the gain is adjusted so that the reference signal becomes constant, and the signal S is processed by the signal processing device 234, whereby the absorption information of the sample can be obtained.

FIG. 21 is a diagram for explaining a case where the automatic self-control system of FIG. 20 is applied to a multi-element detection system.

By providing the automatic gain control system of FIG. 20 corresponding to each detector of the multi-element detector 224M, and switching the output from each control system by the analog switch 238 to take out,
Gain adjustment of the signal for each detector can be made.

FIG. 22 is a diagram for explaining the absorbance difference detection method by the sample hold method. In the figure, 240 is a detection system,
Reference numeral 242 is an amplifier, 244 is a synchronous signal generation circuit, 246 is a synchronous detection circuit, 248a and 248b are sample and hold circuits, 250a and 250b are logarithmic amplifiers, 252 is a synthesis circuit, and 254 is an A / D converter.

The signal detected by the detection system 240 is the amplified synchronous detection circuit 2 after amplification.
At 46, two wavelengths, for example, λ ₁ and λ _2, are separated, sample-held respectively, logarithmically amplified, and subtraction circuit 25
Subtracting by 2 gives the logarithmic value of the ratio of the outputs to the wavelengths λ ₁ and λ ₂ . As described above, this represents the difference in absorbance, that is, the concentration of the sample.
At 54, it is converted into a digital amount and data processing is performed by a calculator or the like.

FIG. 23 is a diagram showing an example in which the sample hold method of FIG. 22 is applied to a multi-element detection system to detect the difference in absorbance based on signals from a plurality of detectors.

In FIG. 23, one set of logarithmic amplifiers and one subtractor are associated with the four detectors, and the switching switch 256 is used.
The logarithmic amplifier is shared by switching using a and 256b, the output obtained from each subtraction circuit is taken out through the analog switch 258, and each A / D converter 254 obtains a digital output.

24 and 25 are views for explaining an electrical direct ratio detection method by frequency component detection, in which 260 is a detector, 262 is a preamplifier, 264 is a signal component separation circuit,
Reference numerals 266 and 268 are filters, 270 and 272 are synchronous rectifier circuits, 274 is a synchronous signal generator, 276 is an adder circuit, 2
Reference numeral 78 is a ratio calculation circuit, 280 is a recorder, 282 is a calculation circuit, and 284 is a sector.

In this method, the sector 284 is divided into four areas as shown in FIG. 25 (a), the area P ₁ is a dark area where no signal passes, and the areas P ₂ and P ₄ are areas where a signal of wavelength λ ₁ passes. , P ₃
The area is an area through which a signal of wavelength λ ₂ is passed, and by rotating this sector, as shown in FIG. 25 (b), a sequence such as D, λ ₁ , λ ₂ , D. Take out the signal.

This signal can be detected as an AC signal having a frequency of λ ₁ of f and a frequency of λ ₂ of 2f by blocking a DC component. Now, as shown in FIG. 24, the detector 260 detects a signal as shown in FIG. 25 (c), and the signals are amplified by the preamplifier 262 and filtered by the filters 266 and 268 that pass the frequencies f and 2f. In this way, signals of λ ₁ and λ ₂ are extracted, respectively. By synchronously detecting this signal by the synchronous rectifier circuits 270 and 272, signals corresponding to the wavelengths λ ₁ and λ ₂ are extracted.

By the way, since the signal of the frequency number f, that is, λ ₁ is superimposed on the signal of the wavelength λ ₂ , that is, the frequency 2f, the component of the wavelength λ ₁ is subtracted and removed by the adder circuit 276 to obtain I ( The signals of λ ₁ ) and I (λ ₂ ) can be separated and extracted, and by calculating these ratios by the ratio calculation circuit 278, the signal corresponding to the difference in absorbance can be extracted and recorded. Record with device 280.

In this way, signals of two wavelengths are allocated as signals of frequencies f and 2f, respectively, and by detecting those frequency components, it is possible to detect signals that are not affected by noise.

FIG. 26 shows an example in which the detection method of FIG. 24 is applied to a multi-element detection system, and preamplifiers, signal component separation circuits, and arithmetic circuits corresponding to the number of multi-element detectors 260M are connected and arranged, Each signal is taken out by sequentially switching by the multiplexer 284.

The above is an example of the case where the detected light intensity is relatively strong and continuous output is obtained, but the extremely weak light measurement method will be described below.

27 and 28 are diagrams for explaining the extremely weak light measurement method. In the figure, 290 is a laser light source, 292 is a chopper, 294 is a photomultiplier (PM), 296.
Is a pulse amplifier, 298 is a pulse height discriminator, 300 is a gate, 302 is a phase shifter, 304 is a gate output generator, 30
Reference numeral 6 is an addition / subtraction counter, and 308 is a recorder.

When detecting light with PM, if the intensity of light to be detected is strong, the output of PM is continuous, and the intensity of incident light can be measured from its DC component. However, when the intensity of the incident light becomes extremely weak, the PM output becomes discrete and the pulse output becomes discontinuous. By counting this pulse output, it is possible to measure extremely weak incident light such as one photon at a time. However, when such extremely weak light is measured, the PM itself emits a noise pulse and thus detects the background. Therefore, it is necessary to remove such background. Therefore, the second
In the example of FIG. 7, the signal light and the background are switched by the chopper, the output detected in each period is subtracted by the addition / subtraction counter to remove the background, and extremely weak incident light is measured.

In FIG. 27, a very weak incident light is detected by the chopper-292.
And chopping is performed and detected by PM294. At this time, the addition / subtraction counter 306 is driven through the phase shifter 302 and the gate signal generator 304 using the switching frequency f ₀ of the chopper as a reference signal. The output of the PM 294 is amplified by the pulse amplifier 296, and then the pulse height is discriminated by the pulse height discriminator 298, and a signal having a certain magnitude or more, that is, a pulse output is added to the addition / subtraction counter through the gate 300. The addition / subtraction counter adds / subtracts the signal chopped by the chopper-292 and the background detection output.

As shown in FIG. 28 (a), the total output of the signal S and the noise N is obtained while the chopper is open, and the background noise N is obtained while the chopper is closed. To do. The gate 300 is synchronized with this chopper, and as shown in FIGS. 28 (b) and (c), the gate of the addition / subtraction counter 306 is such that addition is made while the chopper is open and subtraction is made while the chopper is closed. Take control. By doing so, noise has a property of appearing constant over the entire period, so that noise can be removed from the output of the addition / subtraction counter 306 and the signal S can be detected.

29 and 30 show the case where the detection method shown in FIG. 27 is applied to the dual wavelength detection method. 27th in the figure
The same numbers as in the figure indicate the same contents, and the counters 306b, 3
Reference numeral 06c constitutes an adder / subtractor circuit for wavelengths λ ₁ and λ ₂ , respectively.

Now, the signals shown in FIGS. 30 (a) (b) (c) are applied to the gate control circuit 3
12 to add / subtract counters 306b, 30
Gate 6c. In the period of the gate signal shown in FIG. 30 (a), the signal of wavelength λ ₁ is added / subtracted by the counter 306b.
The signal of wavelength λ ₂ is added by the adder / subtractor counter 306c during the period of the gate signal of FIG.
In the period of the gate signal in FIG.
The background signal is subtracted at 6b and 306c. As a result, signal outputs for the lengths λ ₁ and λ ₂ are obtained from the adder / subtractor counters 306b and 306c, respectively, and the difference in absorbance can be detected by calculating the ratio of these signals in the arithmetic processing unit 310. .

FIG. 31 shows a case in which the method of FIG. 29 is applied to a multi-element detection system, in which the outputs of the addition / subtraction counters 306-1 to 306-n are stored in the memories 314-1 to 314-n and they are sequentially stored. It is possible to measure the difference in absorbance between the respective detectors by taking in the arithmetic processing unit 310 and calculating the ratio calculation of two wavelengths.

FIG. 32 shows the near-infrared absorption spectrum of the upper arm, where I is an example of a man with a small amount of fat, II is an example of a woman with a large amount of fat, III is an absorption spectrum of only fat, and IV is an absorption spectrum of water.

970 due to water in upper arm spectrum of fat woman
The absorption peak at 930 nm derived from fat is clearly seen with the absorption at nm. On the other hand, in a man's arm with little fat, the absorption at 930 nm is seen only as a small shoulder. Relative fat content can be calculated from such spectral differences, and the values correlate well with those actually analyzed.

By the way, when the living body performs normal functions, the supply of oxygen is the most indispensable factor.For example, in myocardial infarction and cerebral infarction, the blood supply is cut off due to the blockage of some blood vessels, resulting in interruption of oxygen supply to tissues. , Irreversible death of cells. Historically, optical measurement was first applied to the measurement of oxygen concentration in living tissues, and since then, the most results have been obtained. In short, photobiological measurement means cytochrome oxidase, myoglobin (Mb), hemoglobin (Hb), pyridine nucleotide (NAD).
It is nothing but the absorbance and fluorescence intensity of the four chromoproteins (Chromophore) of H) traced in vivo.

In the following, cytochrome oxidase, myoglobin (M
b), the hemoglobin (Hb), the absorbance of four chromoproteins of pyridine nucleotide (NADH), and the fluorescence intensity will be briefly described.

FIG. 33 (a) is a diagram showing visible and near-infrared absorption spectra of the oxygenated hemoglobin solution.

The most speculative "spectroscopic oxygen concentration indicator" we have is blood. The blood in the arteries (where there is plenty of oxygen) has a clean red color, while the venous blood with low oxygen looks blackish. This reflects that the color of Hb contained in red blood cells in the blood changes depending on whether or not it is combined with oxygen. The spectrum is as shown in FIG. 33 (a), and if it is detected by using the highly directional imaging system of the present invention and the color change (absorption change) is optically followed, You can know the amount of oxygen.

FIG. 33 (b) is a diagram showing an absorption spectrum of myoglobin in the visible region.

Myoglobin is mainly present in a large amount in mammalian muscle cells and has iron-porphyrin like hemoglobin in blood. It is this protein color that makes fresh pork and beef a nice red color. This protein is about 5 to 10 times more abundant than the cytochromes mentioned above, so that myoglobin absorbs most of the visible light when the muscle is illuminated.

When the muscle begins to contract now, myoglobin first shifts from a state where oxygen is bound (oxygenated myoglobin) to a state where oxygen is not bound (deoxygenated myoglobin). In this case, the longer the contraction time, the greater the deoxygenation. At this time, blood is flowing normally in the muscle. Next, if the blood flow is stopped (constriction of arteries) to cause intramuscular contraction, the rate of deoxygenation of myoglobin increases, and even if the contraction is stopped, there is no simple supply from blood and it cannot be restored. . From this, it can be seen that even in our muscles, when suddenly exerting force or exercising, oxygen consumption becomes large, supply from blood vessels cannot be made in time, and cells become deficient in oxygen. Actually, when the same measurement is performed by a human arm, the behavior greatly differs depending on the age and the presence or absence of training with respect to the exercise load. Therefore, the detailed behavior of the muscle can be known by measuring the absorption of light with the highly directional imaging system of the present invention.

FIG. 34 is a diagram showing the difference between the absorption spectrum and the absorbance in the 700 to 1200 nm region (near infrared) of Hb and Mb. In FIG. 34 (a), the solid line shows the oxygenated type and the broken line shows the deoxygenated type.

There is almost no difference between Hb and Mb. Oxygenated Hb is 93
It has an absorption peak at 0 nm. This absorption intensity is 5
It is 1/40 or less of the absorption at 78 nm. Deoxygenated Hb has absorption peaks at 760 nm and 905 nm. Oxygenation-
Isosorption point in deoxygenation (isosbestic p
oint) is 805 nm, and since the absorption intensity at this wavelength does not depend on the oxygen saturation, it can be used to measure the total hemoglobin amount. Therefore, by obtaining these absorption spectra using the highly directional imaging system of the present invention, the total hemoglobin amount and the like can be accurately obtained.

FIG. 35 is a diagram showing an absorbance spectrum of purified cytochrome oxidase. In the figure, the solid line is the oxidation type and the broken line is the reduction type.

The change in light absorption of cytochrome is an indicator that shows whether the cells have sufficient oxygen or lack of oxygen at that time. This cytochrome is present in all biological tissues, including humans. In fact, all organisms have intracellular microgranules called mitochondria in which this cytolme exists. Therefore, if the change in absorption of this cytochrome, mainly in the visible region, is spectroscopically measured by the highly directional imaging system of the present invention, excess or deficiency of oxygen in the tissue (intracellular) can be known nondestructively, The spectrum can be easily recorded.

FIG. 36 is a diagram showing a spectrum of relative fluorescence intensity of pyridine nucleotide (NADH).

Our body (tissue) emits relatively strong luminescence (fluorescence) in the visible part when it is exposed to ultraviolet light. This fluorescence intensity also sensitively reflects the oxygen concentration in the cells.

Fig. 36 shows the live heart of a mouse in ultraviolet light, in this case 34
It shows the spectrum of fluorescence generated by irradiation with 0 nm, and the fluorescence of 450 to 480 nm is emitted by the reduced form of the low molecular compound pyridin nucleotide contained in the biological tissue, and this also applies to all tissues. Exists. The intensity of this fluorescence increases when the oxygen in the tissue is exhausted. Therefore, by measuring the change in the fluorescence intensity of this substance with the highly directional imaging system of the present invention, the increase or decrease in the amount of oxygen can be estimated.

FIG. 37 shows the oxygen concentration dependence of the above-mentioned indicator, that is, the calibration curve.

In the figure, hemoglobin and myoglobin show how much oxygen is bound in the state where all oxygen is bound and not bound as 100% and 0%, and for cytochrome oxidase and NADH, the ratio of oxidation / reduction is plotted on the vertical axis. There is. If we could use light from this calibration curve to detect what percentage, for example myoglobin was bound to oxygen,
The absolute value of the oxygen concentration in the tissue at that time can be known. Similarly, for example, by shining light on the human head from the outside and detecting a change in the amount of light absorbed by hemoglobin, the amount of oxygen in brain tissue can be known without making a hole in the skull.

In the first state, when myoglobin is 100% oxygenated, and when the oxygen supply is 0 and the change in light absorption is constant, all myoglobin is deoxygenated, and this change is taken as the full scale, thus determining the full scale. For example, the rate of deoxygenation of myoglobin can be obtained at any place, and the oxygen concentration can be converted from the calibration curve into the oxygen concentration.

〔The invention's effect〕

As described above, according to the present invention, it is possible to reliably attenuate and remove the scattered component of the transmitted light from the measurement target that includes the scattered component, and extract the light straight-ahead component that includes only the absorption information. . Therefore, by using the high directivity imaging element and the high directivity imaging apparatus of the present invention, it is possible to dramatically improve the resolution and obtain an optical CT image. When applied to the human body, it is possible to observe only the blood vessel image of the human body, for example, by using the wavelength corresponding to the absorption region of hemoglobin, or the wavelength light corresponding to the absorption wavelength of the nervous system is used. For example, you can observe an image of the nervous system, or if you want to observe something that has a predetermined absorption wavelength, such as brain cells, bones, specific cells, etc., irradiate with light of that absorption wavelength to see the part you want to see. Only the image can be clearly imaged and observed, which can be used for a dramatic improvement in medical technology and the like. In addition, the image forming method of the lens capable of enlarging and reducing the image is the first image forming method, and the holographic image forming method capable of recording and reproducing the stereoscopic image is the second image forming method. Then,
The present invention provides a completely new imaging method that has never existed before. In other words, it is a method that enables an absorption image even if there is a scattering medium in the middle of light propagation. This new third
The invention of the imaging method described in (1) makes it possible to observe an absorption image in a scattering medium, which has been impossible in the past, and it has become possible to measure an optical tomographic image of a living body. It is clear that this new third imaging method can be widely applied not only to optical tomographic image measurement of a living body but also to image observation when there is a scattering medium in the course of light propagation, and it is widely used as a new innovative imaging method in society. Expected to contribute to.

[Brief description of drawings]

FIG. 1 is a diagram showing a plane wave highly directional imaging element of the present invention, FIG. 2 is a diagram showing an embodiment in which the highly directional imaging elements shown in FIG. 1 are bundled in a cylindrical shape, and FIG. FIG. 4 is a diagram showing an example in which a convex lens is provided on the incident surface of the high-directivity image forming system, FIG. 4 is a diagram showing an example in which an optical fiber is provided on the incident surface side of the high-directivity image forming system, and FIG. FIG. 6 is a diagram showing an example in which the sexual imaging system is configured as a multi-channel type, FIG. 6 is a diagram showing the basic configuration of a spherical wave height directivity imaging system, and FIG. 7 is the incident surface side of the optical system of FIG. FIG. 8 is a diagram showing an example in which a convex lens is provided, FIG. 8 is a diagram showing an example in which an optical fiber is provided on the incident surface side of the highly directional imaging system in FIG.
FIG. 10 is a diagram for explaining how to bundle the spherical wave high directional image forming elements, FIG. 10 is a diagram for explaining a high directional image forming system having a rectangular cross section, and FIG. 11 is a separated arrangement so as to be orthogonal to each other. The figure which shows the example which constituted the plane wave high directivity imaging system with the 2 sets of optical plates which were done, FIG. 12 (a) is a figure which shows the spherical wave high directivity imaging system of a rectangular cross section, FIG. 12 (b) is The figure which shows the spherical wave high directivity imaging system comprised by two sets of high directivity optical plates radially arranged so as to diverge at a predetermined angle.
FIG. 13 is a diagram for explaining a method of irradiating a sample with a laser beam, and FIG. 14 is a diagram showing an example of detecting a sample-transmitted light by using the highly directional imaging system of the present invention, FIGS. 15, 16 FIG. 17 is a diagram for explaining the detection method by the highly directional imaging system of the present invention, FIG. 17 is a diagram showing the overall configuration of the optical tomographic imaging apparatus of the present invention, and FIG. 18 is oxygenated myoglobin and desorption. The figure which shows the light absorbency characteristic with respect to the wavelength of oxygenated myoglobin, 1st
FIG. 9 is a diagram for explaining the two-wavelength method and the difference spectrum method,
FIG. 20 is a diagram for explaining automatic gain control in the two-wavelength detection system, and FIG. 21 is a diagram for explaining a case where the automatic self-control system of FIG. 20 is applied to a multi-element detection system.
FIG. 2 is a diagram for explaining the absorbance difference detection system by the sample hold system, FIG. 23 is a diagram showing an example in which the sample hold system of FIG. 22 is applied to a multi-element detection system, and 24.
25, FIG. 25 is a diagram for explaining an electrical direct ratio detection method by frequency component detection, FIG. 26 is a diagram showing an example in which the detection method of FIG. 24 is applied to a multi-element detection system, FIG. ,
FIG. 28 is a diagram for explaining an extremely weak light measurement method, and FIG.
9 and 30 are diagrams for explaining an example in which the detection method shown in FIG. 27 is applied to a two-wavelength detection method, and FIG. 31 is an example in which the method in FIG. 29 is applied to a multi-element detection system. Fig. 32 shows the near-infrared absorption spectrum of the upper arm, Fig. 33
Fig. (A) is a diagram showing visible and near-infrared absorption spectra of oxygenated hemoglobin solution, Fig. 33 (b) is a diagram showing absorption spectra of myoglobin in the visible region, and Fig. 34 is H
b and Mb showing the near-infrared absorption spectrum and the difference in absorbance, FIG. 35 shows the absorbance spectrum of purified cytochrome oxidase, and FIG. 36 shows the pyridyl nucleotide (N
FIG. 37 shows a spectrum of relative fluorescence intensity of ADH),
FIG. 38 is a diagram showing the oxygen concentration dependence of the indicator substance, FIG. 38 is a diagram showing a device configuration for obtaining a conventional light absorption distribution image, and FIG. 39 is a diagram showing another device configuration for obtaining a conventional light absorption distribution image. , 4th
Fig. 0 shows Twersky's scattering theory curve, 41st
FIG. 42 is a view for explaining a conventional transmitted light detection method, 42nd
The figure is a diagram for explaining detection of transmitted light by a fiber collimator. 100 ... Highly directional imaging element, 103 ... Light absorbing material, 1
05 ... Core, 107 ... Clad, 120 ... High directivity imaging system, 121 ... Radiation directing pattern, 123 ... Convex lens, 125 ... Pinhole, 127 ... Optical fiber, 130 ... Spherical wave height directivity Sexual imaging system.

Claims (6)

[Claims] 1. A hollow thin tube having a linear cross-section with a circular or rectangular cross section, the inner wall surface of which is coated with a light absorbing material.
When the aperture diameter is D, the length is 1, and the wavelength of the incident light is λ, the dimensions and shape are l = kD ² / λ (k: proportional constant), and the aperture diameter D is at least larger than the wavelength λ, A highly directional imaging element characterized in that it is possible to observe a Fraunforfer diffraction image due to a plane wave on the exit surface side. 2. An optical fiber comprising a core portion and a cladding portion, the refractive index of the core portion being smaller than the refractive index of the cladding portion, wherein the optical fiber has an aperture diameter of D, a length of 1, and an incident light. When the wavelength of light is λ, the size and shape are l = kD ² / λ (k: proportional constant), the aperture diameter D is made larger than at least the wavelength λ, and the Fraunhofer diffraction by a plane wave is performed on the emission surface side. Highly directional imaging element characterized by making images observable. 3. A plurality of highly directional imaging elements according to claim 1 or 2 are bundled together, and a spatial distribution image of a Fraunforfer diffraction image for each imaging element can be detected. High directivity imaging device. 4. The highly directional imaging element according to claim 1 or 2, wherein the cross section perpendicular to the optical axis continuously increases from the entrance surface to the exit surface, and A highly directional imaging device, which is capable of detecting a spatial distribution image of a Fraunforfer diffraction image. 5. A plurality of apertures formed by each set of optical plate groups, wherein at least two sets of optical plate groups, each of which has a plurality of optical plates whose walls are coated with an absorbing material, are arranged in parallel with each other and are separated from each other. Where D is the diameter, l is the length, and λ is the wavelength of the incident light, the dimensions and shape are l = kD ² / λ (k: proportional constant), and the aperture diameter D is at least the wavelength λ. High directivity, which is characterized by making it larger so that the Fraunforfer diffraction image due to a plane wave can be observed on the exit surface side, and the spatial distribution image of the Fraunforfer diffraction image of each aperture can be detected by multiple apertures. Imaging device. 6. At least two optical plate groups in which a plurality of optical plates whose walls are coated with an absorbing material are arranged so that the wall surfaces are parallel to a line radially radiating from one point, are separated from each other and are orthogonal to each other. , Where each of the plurality of apertures formed by each set of optical plate groups has an incident aperture diameter of D, a length of l, and a wavelength of incident light of λ, then l = kD ² / λ (k: proportional constant ), The entrance aperture D is made larger than at least the wavelength λ, and the Fraunforfer diffraction image due to a plane wave can be observed on the exit surface side. A highly directional imaging device characterized by being able to detect a distribution image.