JPH0675033B2 - Optical measuring method of biological tissue and light source device for measuring the same - Google Patents

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for optically measuring a living tissue, which optically measures the living tissue, and a light source device for the measurement, among medical diagnostic methods.

2. Description of the Related Art Recently, a technique for observing the inside of a living body that does not damage externally (pessimistic blood) has been developed. That is, this observation technology
The scattering, absorption, and emission of light by living tissues utilize the characteristic that each tissue has a characteristic wavelength dependence (dispersion relationship). This observation method is used in observation techniques such as X-ray CT and ultrasonic CT. , The probe of observation was used instead of the X-ray and the ultrasonic wave. In other words, among electromagnetic waves called light, light in the infrared region in particular shows good translucency to living tissue, and therefore, using this kind of light, CT using light becomes possible.

FIG. 2 shows a conventional two-dimensional scanning system for oxygen concentration in a living body using a fiber collimator.

In FIG. 2, 1 is a semiconductor laser and He-Ne which will be described later.
A light source 2 using a laser, 2 is an optical fiber that guides the laser light of the light source 1 to the object 3, 4 is an optical fiber that receives and guides the laser light from the object 3, and 5 and 6 detect light from the optical fiber. A detector and a preprocessing circuit for performing photoelectric conversion and the like. Reference numeral 7 is an A / D converter for converting the analog detection signal output from the pre-processing circuit 6 into a digital signal, 8 is a computer for analyzing the characteristic distribution of the output through the interface 9, and 10 is its monitor. Reference numeral 11 is a motor driver that drives the optical fibers 2 and 4 in two dimensions via the motor 12. The preprocessing circuit 6 is a semiconductor laser.
Two systems are provided corresponding to the He-Ne laser, and two motors 12 are also provided corresponding to the x and y directions.

Now, in this two-dimensional scanning system, the light source is the same as the A1GaAs / GaAs semiconductor laser with an oscillation wavelength of 780 mm.
A 632.8 mm He-Ne laser is used. Therefore, although the absorption distribution of light is measured by scanning the fiber collimator in a two-dimensional plane, for example, fat and tumor tissue can be distinguished and the distribution can be obtained depending on the wavelength dependence of the absorption of light. However, the wavelength dependence when the two light sources described above are used is the wavelength dependence of scattering, and therefore there is a drawback that it is difficult to obtain contrast.

By the way, the spectroscopic measurement of a biological system can be treated as a spectroscopic measurement of a heterogeneous system essentially including a scatterer. That is, when light is transmitted through the living body, the wavelength dependence of the transmittance is due to scattering and absorption, and their contributions can be treated as being independent of each other. Substances such as water, fat, and proteins that make up biological tissues have absorption lines (bands) peculiar to each substance in the visible to infrared wavelength range. In addition, proteins also have absorption lines that are unique to each of many types, and it is possible to identify living tissues by utilizing these absorption lines.

Using a protein as an example, the measurement method is explained.By comparing the absorption rate at the wavelength of the desired absorption line with the absorption rate at the wavelength in the immediate vicinity, we can theoretically obtain knowledge of the abundance and distribution of the desired protein. To be Since there are generally a plurality of absorption lines for each protein, measuring at a plurality of wavelength points improves the measurement accuracy of concentration and distribution. Further, if the measurement wavelength can be scanned, the shape of the absorber can be known, and the accuracy of measuring the absorptance can be expected to improve. Further, even in the light emission peculiar to each substance after absorbing light, similar identification of composition and knowledge of distribution can be obtained.

Although living organisms are perfect scatterers, Rayleigh scattering is a major contributor to light scattering, and multiple scattering is more dominant than single scattering. Empirically, the reciprocal of the wavelength is 4
The scattering coefficient proportional to the 6th power is shown. In the example of utilizing the dispersion relation of light scattering and using light of a plurality of wavelengths, detection of tumor tissue and measurement of oxygen concentration distribution in the tissue are known.

When measuring the absorptance, simply measuring the absorption line existing in the long wavelength region is more advantageous than measuring the absorption line in the short wavelength region because the effect of light attenuation due to scattering is reduced. .
For example, there is a difference of about 10 in the amount of transmitted light between wavelengths of 600 nm and 1000 nm.

However, the situation is different when the transmitted light is detected by narrowing the light to a small aperture (<1 mm). In the case of this measurement, while light is scattered, light of a specific wavelength is absorbed by proteins, water, and fat at a specific wavelength, but the light that keeps the incident direction and the light that goes straight are those substances. Not absorbed by. On the contrary, the scattered light has a long optical path, so that it is highly absorbed and its intensity decreases. As a result, the light having a wavelength in the vicinity of the absorption line has an intensity distribution in which after entering, the light hardly spreads and then exits from the opposite side. By utilizing this property, it is possible to scan light on the measurement object and obtain knowledge of the state of two-dimensional and three-dimensional distribution. In principle, it can be applied to optical CT. It is possible. In detail, if the light transmitted through the measurement object can be detected, the shorter the wavelength, the smaller the spread of the light and the better the spatial resolution. However, in order to improve the spatial resolution, attenuation of light intensity due to scattering becomes large, so that there is a wavelength under each optimum condition at the time of measurement.

As described above, in the "as-is observation" of a living body using light, visible to near-infrared light is going to play a very important role.

Problems to be Solved by the Invention When observing and measuring a living body as described above, 500 to 1500 nm
It is necessary to use a light source which is variable and has a high brightness (for example, a laser of single wavelength oscillation has a wavelength of about 5 to 20 mw) in the wavelength range between the two. However, at present, there is no suitable light source. That is, when white light such as halogen light is used after being separated by a spectroscope, the brightness of the light after the separation is low, the measurement takes time, and sufficient resolution cannot be obtained. Therefore, although lasers with high brightness (power density) are attracting attention, generally known solid-state and gas lasers have fixed wavelengths, and thus are not suitable for measurement with different wavelengths. Also,
In the case of conventional dye laser, the scanning range of wavelength is narrow,
It is necessary to change many kinds of dyes, and the life of dyes is generally short, which is not appropriate. In addition, solid,
Gas and dye lasers also have the drawback of being large (100 kg or more) and expensive.

On the other hand, a semiconductor laser has a wide oscillation wavelength range, is small (usually 1 g or less), and has low power consumption.
It fits the purpose.

When semiconductor lasers are examined, currently available semiconductor lasers can be roughly classified into three types. In other words, these types are A1GaAs / GaAs system, InGaAsP / InP
System and A1GaInP / GaAs system, but the oscillation wavelength ranges are 780 to 900 nm1, 100 to 1600 nm5, and 80 to 670 nm, respectively.

However, in the conventional semiconductor laser, 1) the wavelength region of 900 to 1100 nm, which is frequently used in biological tissue measurement, is blank. 2) The oscillation wavelength can be changed depending on the composition or structure of the active layer of the device. It was decided for each element, and there were two problems: it could not be changed significantly under external operating conditions such as current injection.

In addition, in the conventional semiconductor laser, the wavelength cannot be changed in a wide range with one element, so a plurality of semiconductor laser elements are used instead of operating the wavelength. For each change, for example, a troublesome adjustment of the optical axis is required.

Means for Solving the Problems In order to solve the problems described above, the present invention takes the following technical solutions. That is, 1) the substrate is GaAs, and the material of the clad layer and the ohmic contact layer is A1xGa1 _- xAs that lattice-matches with the substrate,
GaxIn in which the material forming the active layer has a lattice mismatch with the substrate
A semiconductor laser using _1- xAs (0 ≦ x ≦ 0.5) is used as a light source. This semiconductor laser can obtain an oscillation wavelength between 780 and 1100 nm by changing the composition X of the active layer.

2) Instead of using a plurality of laser elements, a multi-stripe type laser is used as a light source. In this laser, the G of the active layer of the GaInAs / A1GaAs system laser described above
The In composition of axIn _1- xAs can be changed for each stripe. That is, in such a stripe structure, since the oscillation wavelengths are different between the stripes, it is possible to perform scanning at different oscillation wavelengths although they are discontinuous. That is, since the distance between the stripes can be set to about 200 μm, the adjustment of the optical axis becomes unnecessary or insignificant, and the optical system becomes very simple.

Operation According to the above-described configuration of the present invention, it becomes easy to identify a substance in a living body tissue and measure its distribution by scanning a plurality of laser beams having different wavelengths in the visible to near-infrared light region. Further, according to such a measuring method, the types of substances that can be identified can be expanded with respect to the current situation, and in the tissue distribution measurement, the spatial resolution can be improved and the measurement time can be shortened.

Embodiment Hereinafter, details of an embodiment of the present invention will be described with reference to the drawings.

By the way, when a GaInAs / A1GaAs laser is also used as a light source and four-point measurement with wavelengths of 900 and 1000 nm is performed, the contrast is improved. This is because the difference in the amount of light extinction due to scattering between different living tissues becomes clear due to the expansion of the wavelength range. Also, fat is 930nm and water is 970nm.
It is well known that there is an absorption line in and a clearer tissue distribution can be obtained by using light of this wavelength.

The conventional biological tissue measuring system shown in FIG.
In addition to an A1GaAs / GaAs semiconductor laser with an oscillation wavelength of 780 nm and a He-Ne laser with an oscillation wavelength of 632.8 nm, a GaInAs / A1GaAs semiconductor laser with an oscillation wavelength of 900 nm and 1000 nm according to the present invention is used together. When four-point measurement was performed, high contrast was obtained. This is because the wavelength range is expanded and the difference in the extinction amount due to scattering in different living tissues is increased.

The absorption line of fat is at 930 nm and the absorption line of water is at 970 nm. Therefore, by using light of these wavelengths, a clearer tissue distribution can be observed.

Furthermore, by using the A1GaInP / GaAs-based semiconductor laser in the red region of visible light and the InGaAsP / InP-based infrared semiconductor laser together, the absorption of light in living tissue and the wavelength dependence of radiation can be measured in a wider wavelength range. Will be possible.

FIG. 1 is a cross-sectional view of a multi-stripe type laser according to the present invention which obtains various kinds of light as described above, 101 is an active layer, 102, 103 are cladding layers, and 104 ₁ ... 104 n are a plurality of light emitting portions. .

This active layer is GaxIn _1- xAs. As shown in FIG. 3, the In composition is 0 on the left side and increases toward the right. In the case of this material, the band gap decreases as the In composition increases, and the oscillation wavelength as a laser increases. For example, in a single quantum well structure, the quantum well width is 7 nm and x = 0.2.
The oscillation wavelength is about 980nm. When the stripe interval is 200 μm, 11 stripes have a width of 2 mm.
In the biometric measurement, the beam diameter of light is 1 because of scattering in the tissue.
Since ~ 2mm is sufficient, this can be regarded as the same light source.
Of course, the In composition distribution and the number of stripes may be changed and used as needed.

Returning to FIG. 2, a measurement example using the multi-striped laser device of the present invention, which has an oscillation wavelength of 860 to 1000 nm and can obtain 11 wavelengths at equal intervals, is shown. Absorption lines of fat and water in this range are present at 930 and 970 nm, respectively. In addition, scattering in the living body in this region is low, and light transmitted through a thickness of several cm to several tens of cm (a size of mouse, rabbit, or human head) can be detected. When this multi-striped laser is used as a light source for the examination of breast cancer in the system shown in FIG. 2, a tumor of several mm can be detected within the examination time of 1 minute.

EFFECTS OF THE INVENTION As described above, the present invention, in the conventional light source, lacks in brightness,
Alternatively, since the wavelength of light that can be used is limited, identification of a biological tissue substance, which has been difficult to realize, and fine distribution measurement are facilitated. Further, since the light source according to the present invention has high brightness, it can be measured in a short time. Can be finished. Therefore, according to the present invention, it is possible to obtain an optical measurement method that can be used for observing a substance in a living body such as medical diagnosis such as tumor screening and observing an oxygen concentration distribution in living tissue in a living state. You can

[Brief description of drawings]

FIG. 1 shows a semiconductor light emitting device of the present invention, (a) is a sectional view thereof, (b) is a diagram showing the In composition of an active layer, and (c) is a diagram showing changes in emission wavelength corresponding to stripe positions. FIG. 2 is a block diagram showing a conventional measuring system for biological tissues. 101 ... Active layer, 102, 103 ... Clad layer, 104 ₁ to 104n
...... Light emitting part.

Claims (7)

[Claims] 1. A substrate made of GaAs, at least a material forming an active layer is Ga _X In _1-X As (0 ≦ x ≦ 0.5), and a material forming a cladding layer and an ohmic contact device is A 1 _X G
a _1-X As, a semiconductor light-emitting device that emits light in the visible to red to near-infrared wavelength range is used as the light source, and the light from this light source is applied to the living body to absorb and reflect light emitted by living tissue. An optical measurement method for living tissue, which comprises measuring the wavelength dependence of 2. GaAs is the substrate, and (A1xGa _1-X ) yIn _1- yP
A light emitting device using (0 ≦ x · y ≦ 1) as a constituent material, wherein the clad layer has a band gap larger than that of the active layer by about 0.25 eV and has a composition lattice-matched to the GaAs substrate. Yes (A1 × Ga _1- x) _0.5 In _0.5 P (0 ≤ x ≤
2. The optical measuring method for a biological tissue according to claim 1, wherein the semiconductor light emitting device of 1) is used as a measuring light source that emits red light in the visible region. 3. A semiconductor light emitting device, wherein InP is a substrate, InGaAsP is used as a constituent material, and a clad layer has a band gap larger than that of an active layer by about 0.25 eV as a light source for measurement. The optical measuring method of a biological tissue according to claim 1. 4. A substrate made of GaAs, at least a material forming an active layer is Ga _X In _1-X As (0 ≦ x ≦ 0.5), and a material forming a cladding layer and an ohmic contact layer is A 1 _X G
a _1-X Ga _1-X As, which is a semiconductor light-emitting device having a plurality of light-emitting units capable of emitting light in the visible to red wavelength region and the near-infrared wavelength region and independently emitting light. A light source device for measuring biological tissue, wherein composition ratios x of the active layer constituent materials are different between the active layers of the light emitting section, and light having different wavelengths is emitted between the light emitting sections. 5. The light source device for measuring a biological tissue according to claim 4, wherein the light emitting portion is installed in a region that can be regarded as within the same optical axis. 6. By changing the location of the injected current,
The light source device for measuring biological tissue according to claim 4, wherein the emission wavelengths of the plurality of light emitting units can be changed. 7. An optical measuring method of a biological tissue, which comprises measuring the wavelength dependence of light absorption, reflection and emission of the biological tissue by using the light source device according to claim 4.