Tissue identification device, tissue identification system, method of identifying tissue, and storage medium

A control section as a tissue identification device includes: an absorbance ratio calculating section configured to calculate the ratio of an absorbance indicated by a transmitted portion of first inspection light transmitted through biological tissue to an absorbance indicated by a transmitted portion of second inspection light transmitted through the biological tissue; and an identification information generating section configured to generate identification information indicative of the type or state of the biological tissue by determining within which of a plurality of preset numerical ranges the ratio falls.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a U.S. National Stage Application of International Patent Application No. PCT/JP2019/017863, filed on Apr. 26, 2019, which claims priority to Japanese Patent Application No. 2018-090871, filed on May 9, 2018.

TECHNICAL FIELD

The present invention relates to a device configured to identify biological tissue, a tissue identification system, a method of identifying biological tissue, and an endoscope system.

BACKGROUND ART

There is a known technique to determine the type or state of biological tissue, in particular, whether or not there is a tumor such as a cancer, by means of absorbance analysis. For example, Patent Literatures 1 to 3 each disclose a technique involving: measuring an absorbance spectrum in a broad infrared range including near-infrared light by Fourier Transform Infrared Spectroscopy (FTIR); and determining whether or not there is cancer tissue based on the absorbance spectrum.

The use of such an optical process makes it possible to identify biological tissue noninvasively. Furthermore, by analyzing the obtained absorbance spectrum in accordance with a predetermined algorithm, it is possible to obtain an identification result which is objective and is not based on the subjective view of an inspector.

CITATION LIST

Patent Literature

SUMMARY OF INVENTION

Technical Problem

However, according to the techniques using FTIR disclosed in Patent Literatures 1 to 3, an absorbance spectrum in a broad wavelength range is acquired and the shape of the acquired absorbance spectrum in its entirety is analyzed; therefore, the identification requires processing a large amount of information. This increases the time for biological tissue to be identified.

An object of an aspect of the present invention is to achieve, for example, a biological tissue identification device that is capable of obtaining a result of identification of biological tissue without having to process a large amount of information.

Solution to Problem

In order to attain the above object, a tissue identification device in accordance with an embodiment of the present invention includes: a calculating section configured to acquire a first measured value and a second measured value and calculate a ratio of the first measured value to the second measured value or a reciprocal of the ratio; and an identification information generating section configured to generate identification information indicative of a type or a state of biological tissue by determining within which of a plurality of preset numerical ranges the ratio or the reciprocal calculated by the calculating section falls, wherein the first measured value is a transmittance, a reflectance, or an absorbance indicated by a transmitted portion of first inspection light transmitted through the biological tissue or a reflected portion of first inspection light reflected from the biological tissue, the second measured value is a transmittance, a reflectance, or an absorbance indicated by a transmitted portion of second inspection light transmitted through the biological tissue or a reflected portion of second inspection light reflected from the biological tissue, and the first inspection light and the second inspection light have respective different peak wavelengths in a range of from 2 μm to 20 μm, inclusive.

A method of identifying tissue in accordance with an embodiment of the present invention is a method including the steps of: applying, to biological tissue, first inspection light and second inspection light having respective different peak wavelengths in a range of from 2 μm to 20 μm, inclusive; acquiring a first measured value and a second measured value, the first measured value being indicative of a transmittance, a reflectance, or an absorbance indicated by a transmitted portion of the first inspection light transmitted through the biological tissue or a reflected portion of the first inspection light reflected from the biological tissue, the second measured value being indicative of a transmittance, a reflectance, or an absorbance indicated by a transmitted portion of the second inspection light transmitted through the biological tissue or a reflected portion of the second inspection light reflected from the biological tissue; calculating a ratio of the first measured value to the second measured value or a reciprocal of the ratio; and outputting identification information to an output device, the identification information being information that is generated by determining within which of a plurality of preset numerical ranges the ratio or the reciprocal falls and that is indicative of a type or a state of the biological tissue.

An endoscope system in accordance with an embodiment of the present invention includes: a first light source configured to emit inspection light having a peak wavelength in a range of from 2 μm to 20 μm, inclusive; a second light source configured to emit visible light; a first optical fiber configured to guide the inspection light emitted from the first light source; a second optical fiber configured to guide the visible light emitted from the second light source; a first light receiving section configured to receive a transmitted portion of the inspection light transmitted through biological tissue or a reflected portion of the inspection light reflected from the biological tissue; and a second light receiving section configured to receive a transmitted portion of the visible light transmitted through the biological tissue or a reflected portion of the visible light reflected from the biological tissue, the first optical fiber and the second optical fiber being arranged coaxially with each other.

An inspection method in accordance with an embodiment of the present invention includes the steps of: applying, to biological tissue, first inspection light and second inspection light which have respective different peak wavelengths in a range of from 2 μm to 20 μm, inclusive; and receiving, by a light detector, transmitted portions of the first inspection light and the second inspection light transmitted through the biological tissue or reflected portions of the first inspection light and the second inspection light reflected from the biological tissue, wherein the first inspection light and the second inspection light each contain a main pulse and a subpulse, and in the step of receiving, a time for which the light detector is allowed to receive light is limited so that at least part of light resulting from the subpulse is not received.

Advantageous Effects of Invention

An aspect of the present invention makes it possible to obtain a result of identification of biological tissue without having to process a large amount of information.

DESCRIPTION OF EMBODIMENTS

The following description will discuss an embodiment of the present invention in detail. First, a technical idea of the present invention is discussed. The inventors of the present invention have analyzed absorbance spectra obtained as a result of applying light of various wavelengths to biological tissue. As a result, the inventors of the present invention have found that, by applying, to biological tissue, mid-infrared rays of at least two wavelengths having respective different peak wavelengths in the range of from 2 μm to 20 μm, inclusive and calculating the ratio between the resulting absorbances, it is possible to identify the biological tissue.

FIG.1is a chart showing an example of absorbance spectra obtained by applying mid-infrared rays to lung tissue. Of the absorbance spectra shown inFIG.1, the absorbance spectra indicated by sign81are absorbance spectra of normal tissue, and the absorbance spectra indicated by sign82are absorbance spectra of cancer tissue. Note that the absorbance spectrum measurement was carried out a plurality of times on each tissue. Also with regard to the absorbance spectra discussed in the following descriptions, the measurement was carried out a plurality of times on each tissue. As a result of the analysis of such two types of absorbance spectra, the inventors of the present invention have made the following findings.There is a wavelength range in which the absorbance is unlikely to change irrespective of the type or state of biological tissue (such a wavelength is referred to as “reference wavelength”). This reference wavelength range is a narrow range equivalent to a peak in an absorbance spectrum. In the case of the example shown inFIG.1, an accurate evaluation can be made by employing a wavelength which is “equivalent to a peak” as the reference wavelength. On the contrary, for example, in the case of the example shown inFIG.12(cerebellar tissue), the absorbance at each wavelength which is “equivalent to a peak” differs greatly between normal tissue and cancer tissue, which makes it difficult to make an accurate evaluation. In such a case, an accurate evaluation can be made by using, as the absorbance at a reference wavelength, the average of the absorbances at reference wavelengths of respective types of tissue. Note, however, that the wavelength set as the reference wavelength may be a wavelength corresponding to a dip in an absorbance spectrum or may be a wavelength corresponding to a flat portion of an absorbance spectrum, provided that the wavelength is one at which the absorbance is unlikely to change irrespective of the type or state of biological tissue.There is a wavelength range in which the absorbance is likely to change depending on the type or state of biological tissue (such a wavelength is referred to as “discrimination wavelength”). In the example shown inFIG.1, the range represented by arrow83A (8.06 μm to 8.70 μm) and the range represented by arrow83B (8.75 μm to 10.05 μm) are the discrimination wavelength ranges.Light of a reference wavelength (referred to as “reference inspection light” (second inspection light)) is applied to biological tissue, and the absorbance indicated by a transmitted portion of the reference inspection light transmitted through the biological tissue or a reflected portion of the reference inspection light reflected from the biological tissue is used as a reference absorbance (second measured value). Light of a discrimination wavelength (referred to as “discrimination inspection light” (first inspection light)) is applied to biological tissue, and the absorbance indicated by a transmitted portion of the discrimination inspection light transmitted through the biological tissue or a reflected portion of the discrimination inspection light reflected from the biological tissue is used as a discrimination absorbance (first measured value). The ratio of the discrimination absorbance to the reference absorbance (i.e., discrimination absorbance/reference absorbance) or the reciprocal of the ratio (reference absorbance/discrimination absorbance) differs depending on the type or state of biological tissue.The following is an explanation from a different point of view. The discrimination absorbance obtained by applying discrimination inspection light to biological tissue differs depending on the type or state of the biological tissue (irradiation target) to a greater extent than the reference absorbance obtained by applying reference inspection light to the biological tissue.

By presetting the range of values that the ratio of discrimination absorbance to reference absorbance (this ratio is referred to as “absorbance ratio”) (or the reciprocal of the absorbance ratio) can take for each type of biological tissue or for each state of biological tissue, it is possible to identify the type or state of to-be-inspected biological tissue by determining within which of the plurality of the preset numerical ranges the measured absorbance ratio (or the reciprocal of the absorbance ratio) falls.

A reason why the absorbance ratio is used instead of the absolute value of the discrimination absorbance is to increase identification accuracy. In a case where laser light is applied to biological tissue and absorbance is measured, the measured absorbance varies also depending on, for example, the angle of incidence of light, conditions in which light is applied, the thickness of sample S, and the like. Therefore, in order to appropriately discern differences in the absorbance spectrum in the discrimination wavelength range, it is preferable to use the ratio of the discrimination absorbance to the reference absorbance which is measured under the identical irradiation conditions, instead of the absolute value of the discrimination absorbance.

Note that the following description will discuss embodiments in which the ratio of discrimination absorbance to reference absorbance is used as-is instead of using the reciprocal of the ratio. In a case where the reciprocal (reference absorbance/discrimination absorbance) of the ratio is used, it is only necessary that the foregoing plurality of numerical ranges be set so as to correspond to the ranges of values that the reciprocals can take.

FIG.1shows a reference wavelength A (8.74 μm), a reference wavelength B (9.73 μm), a discrimination wavelength A (8.28 μm), and a discrimination wavelength B (9.26 μm). In order to identify biological tissue, it is only necessary to use (i) an absorbance (reference absorbance) at at least one reference wavelength and (ii) an absorbance (discrimination absorbance) at at least one discrimination wavelength included in a wavelength range adjacent to the reference wavelength.

For example, the ratio of the absorbance at the discrimination wavelength A to the absorbance at the reference wavelength A (this ratio is absorbance ratio) is calculated for the absorbance spectrum of normal tissue and for the absorbance spectrum of cancer tissue. In the case of the example shown inFIG.1, the absorbance ratio for the normal tissue is greater than the absorbance ratio for the cancer tissue. Therefore, by finding and setting in advance the range of values that each of these absorbance ratios can take, it is possible to determine whether to-be-inspected biological tissue contains cancer tissue or not by determining whether the measured absorbance ratio is included in the range of values that normal tissue can take or in the range of values that the cancer tissue can take. Note that there are also cases in which the absorbance ratio for normal tissue is smaller than the absorbance ratio for cancer tissue.

In the example shown inFIG.1, in a case where the reference wavelength A and the discrimination wavelength A are used and in a case where the reference wavelength A and the discrimination wavelength B are used, the value at the border between the range of values that the normal tissue can take and the range of values that the cancer tissue can take (such a value is “threshold”) can be set to 0.986. In this instance, in a case where the absorbance ratio is smaller than 0.986, the biological tissue can be determined as cancer tissue.

According to conventional techniques, whether biological tissue contains cancer tissue or not is determined by comparing the waveform of the absorbance spectrum of the biological tissue with waveforms stored in a database. In contrast, according to the present invention, the identification of biological tissue is carried out by: applying mid-infrared rays of at least two wavelengths having respective peak wavelengths in the range of from 2 μm to 20 μm, inclusive; and identifying the biological tissue based on the ratio between the resulting absorbances. This eliminates the need for the acquisition of absorbance spectra over a broad wavelength range, and makes it possible to shorten the time for absorbance measurement. Furthermore, since the biological tissue can be identified based on the absorbance ratio, only a small amount of information needs to be processed to carry out identification. This makes it possible to shorten operation time. Furthermore, since biological tissue is identified based on the absorbance ratio, it is possible to carry out objective identification which is not based on the subjective view of an inspector. The number of preset ranges of values that the absorbance ratios can take may be two or three or more. For example, numerical ranges for three or more stages may be set corresponding to the degrees of malignancy of cancer.

The findings described so far apply also to (1) the relationship between the transmittance of reference inspection light transmitted through biological tissue and the transmittance of discrimination inspection light transmitted through the biological tissue and (2) the relationship between the reflectance of reference inspection light reflected from biological tissue and the reflectance of discrimination inspection light reflected from the biological tissue. This is because absorbance, transmittance, and reflectance can be converted into one another. In Embodiment 1, examples in which absorbance is used are only mentioned.

(Configuration of Biological Tissue Identification System1)

FIG.2illustrates a configuration of a biological tissue identification system1in accordance with Embodiment 1. The biological tissue identification system1identifies biological tissue contained in a sample S by: applying mid-infrared light to the sample S on a sample stage20; and measuring the absorbance of light transmitted through the sample S. The biological tissue contained in the sample S may be tissue taken from a human or may be tissue taken from a non-human animal such as a mouse or a rat.

A light source10for use in the biological tissue identification system1is a laser light source that selectively oscillates mid-infrared light having a specific peak wavelength in the range of from 2 μm to 20 μm (i.e., a light source capable of switching wavelengths). In order to increase the accuracy and efficiency of absorbance measurement, it is preferable to use, as the light source10, a light source including a quantum cascade laser that oscillates high-intensity mid-infrared laser light or a light source including an optical parametric oscillator (OPO).

Since laser light is used as inspection light, it is possible to use a high-intensity beam. This eliminates the need for signal averaging and the like, makes it possible to obtain a high S/N ratio, and makes it possible to carry out measurement in a short time. Furthermore, the laser light source enables narrow-linewidth wavelength sweeping; therefore, high wavelength resolution can also be achieved. In addition, the laser light is advantageous also in that the laser light is coherent light and can be focused to its diffraction limit and that high spatial resolution can also be obtained. Furthermore, in a case where an OPO or a quantum-cascade laser is used, the size of the light source10can be reduced, making it possible to reduce the total size of the device.

The light source10generates laser light100by converting excitation light101, which is pulsed light shorter in wavelength than mid-infrared light and which is oscillated from a excitation light source11, into long-wavelength light and concurrently amplifying the pulsed light through an OPO12. Optical parametric oscillation is disclosed in, for example, Japanese Patent Application Publication, Tokukai, No. 2010-281891.

The excitation light source11is particularly preferably a Q-switched Nd:YAG laser (oscillation wavelength: 1.064 μm) or a Q-switched Yb:YAG laser (oscillation wavelength: 1.030 μm), each of which is capable of oscillating pulsed excitation light101which is shorter in wavelength than mid-infrared light. These excitation light sources are capable of allowing a switching operation to take place automatically with use of a saturable absorber. Therefore, the use of the Q-switched Nd:YAG laser or Q-switched Yb:YAG laser as the excitation light source11makes it possible to simplify and reduce the sizes of the excitation light source11and the configuration for controlling the excitation light source11. In Q-switched oscillation, the excitation light101can be oscillated with, for example, a pulse width of about 8 ns at a pulse repetition frequency of 10 Hz or higher.

FIG.3schematically illustrates a configuration of the OPO12. The OPO12is arranged such that a non-linear optical crystal123is disposed between an entrance-side half mirror121and an exit-side half mirror122. Excitation light101that has passed through the entrance-side half mirror121enters the non-linear optical crystal123, is converted to light having a wavelength longer than that of the excitation light101, and, when the light is reflected and confined between the entrance-side half mirror121and the exit-side half mirror122, the light is amplified by optical parametric amplification. The amplified light passes through the exit-side half mirror122, becomes laser light100, and is outputted. Note that, for convenience of illustration, the direction of the laser light100oscillated from the OPO12and the direction of the excitation light101are different inFIG.2; however, these directions are adjusted appropriately by using a reflector.

As the non-linear optical crystal123, AgGaS2that is suitable for this kind of wavelength conversion is used under the condition of phase matching. By adjusting the type and matching conditions of the non-linear optical crystal123, it is possible to adjust the wavelength (oscillation wavelength) at which the laser light100oscillates. As the non-linear optical crystal, it is also possible to use GaSe, ZnGeP2, CdSiP2, LiInS2, LiGaSe2, LiInSe2, LiGaTe2, or the like. The laser light100emitted from the OPO12has a repetition frequency and a pulse width (for example, about 8 ns) that correspond to the excitation light101. This short pulse width achieves a high peak power of 10 W to 1 kW.

The oscillated laser light100is split into two portions by a beam splitter15, and one of the two portions travels toward the sample S fixed on the sample stage20. The other of the two portions is used for monitoring, and is detected at a monitor light detector16. With this, even if the intensity of the laser light100itself changes, such a change can be recognized from output of the monitor light detector16.

The laser light100which travels toward the sample S goes through a condenser lens17and is thereby adjusted to have a small beam spot size on the sample S and to irradiate a specific area of the sample S. The beam spot size on the sample S is, for example, preferably about 10 μm in diameter. A beam spot having such a size makes it possible to apply laser light on a per-cell basis.

The sample stage20has an opening that allows passage of transmitted light100A (a transmitted portion of the laser light100transmitted through the sample S). The transmitted light100A, after passing through the opening, is detected at a light detector18. Furthermore, the sample stage20is capable of moving two-dimensionally relative to the optical axis of the laser light100. This adjusts the area to be irradiated with the laser light100on the sample S.

There is also provided an image capturing section21which is for capturing an image of a region that includes the area of the ample S irradiated with the laser light100. The image capturing section21is provided on the same side of the sample S as the light source10. Note that an optical element capable of reducing the beam spot size of the laser light100can substituted for the condenser lens17. A pinhole or the like may be used instead of the condenser lens17.

A computer30is used to carry out overall control of the biological tissue identification system1. The computer30includes a control section (tissue identification device)31(CPU), a display section32, and a storage section33. The display section32is a display which displays various kinds of information and measurement results. The storage section33is composed of a hard disk or a semiconductor memory each of which stores various kinds of data. The computer30also includes an input section34which receives user operations and which is a touchscreen, a keyboard, a mouse, and/or the like.

FIG.4is a functional block diagram illustrating a configuration of the control section31. As illustrated inFIG.4, the control section31includes: a light source control section41which controls the light source10; an absorbance calculating section42which calculates discrimination absorbance and reference absorbance; and an absorbance ratio calculating section43which calculates the ratio of discrimination absorbance to reference absorbance. The control section31further includes: an organ determining section44; an identification information generating section45; and a measurement position adjusting section46.

The organ determining section44determines from which organ biological tissue in the sample S is derived, by comparing (i) an absorbance spectrum indicated by light transmitted through the biological tissue in the sample S and (ii) absorbance spectra for a plurality of pieces of tissue derived from a plurality of types of organs pre-stored in the storage section33(organ determination).

The identification information generating section45identifies the type or state of to-be-inspected biological tissue by determining within which of a plurality of preset numerical ranges the absorbance ratio falls. The identification information generating section45generates identification information indicative of the type or state of the biological tissue, and outputs the identification information to an output device. The output device is, for example, the display section32, but may be any device such as a speaker or a printer, provided that a user can check the identification result via the output device.

The type of biological tissue identified by the identification information generating section45may mean, for example, whether the biological tissue is normal tissue, a benign tumor, or cancer tissue, or may mean the form of the biological tissue in the progress in which the biological tissue becomes cancerous (stage in the carcinogenesis process). The type of the biological tissue is not limited to cancer, and may mean the form (state) of tissue in which there is an abnormality. That is, in the present specification, determining whether the to-be-identified biological tissue contains cancer tissue or not can be considered subordinate to determining whether there is an abnormality or not in the biological tissue. Thus, the identification information generating section45can be said to generate identification information indicative of whether there is an abnormality or not in the biological tissue by determining within which of the plurality of numerical ranges the absorbance ratio falls.

In a case where the to-be-identified biological tissue is a tumor, the identification information generating section45may identify the histological type of the tumor. In a case where the to-be-identified biological tissue is cancer tissue, the identification information generating section45may identify whether the cancer tissue is metastatic cancer tissue or primary cancer tissue. The identification information generating section45may identify from which organ the to-be-identified biological tissue is derived. Carrying out each of such types of identification is included in the definition of identifying the “type” of biological tissue. The state of the biological tissue means, for example, in a case where the biological tissue is cancer tissue, the degree of malignancy of the cancer.

As such, identification in accordance with the present invention can be carried out on any type or state, provided that the type or state of biological tissue can be associated in advance with the range of values that the absorbance ratio for the biological tissue can take.

The measurement position adjusting section46adjusts the position of the sample stage20relative to the optical axis of the laser light100. This adjustment makes it possible to adjust the position on the sample S which position is to be irradiated with the laser light100(i.e., measurement position).

The light detector18and the monitor light detector16can each be, for example, an HgCdTe infrared detector cooled with liquid nitrogen. The HgCdTe infrared detector is capable of receiving the laser light100or the transmitted light100A whose wavelength is within the foregoing range and outputting the intensity of the received light as electrical signal. In so doing, by causing the excitation light source11to oscillate the excitation light101in the form of pulses and by extracting outputs of the light detector18and the monitor light detector16in synchronization with the pulses, it is possible to detect the laser light100with a high S/N ratio.

Furthermore, by recognizing in advance the relationship between the intensity detected at the monitor light detector16and the intensity detected at the light detector18when light transmittance is 100% (when the sample S is absent), even if the intensity of the laser light100changes over time, it is still possible to properly calculate the light transmittance of the sample S based on the intensity detected at the monitor light detector16and the intensity detected at the light detector18. Note that the monitor light detector16is not essential in a case were the laser light100does not undergo significant temporal changes and the absorbance can be calculated only from the intensity detected at the light detector18in practice.

The above-described biological tissue identification system1can be realized as a microscope system. In this case, a stage of the microscope may be used as the sample stage20. In a case where the sample S is visually checked, an objective lens and an eye lens of the microscope can be used.

(Flow of Process Carried Out by Biological Tissue Identification System1)

FIG.5is a flowchart showing an example of a flow of a process carried out by the biological tissue identification system1. The following description will discuss an example of determining which tissue, among normal tissue, adenoma, fibroadenoma, and cancer tissue, is contained in biological tissue in the sample S.

In a case where it is known that the biological tissue in the sample S is derived from a certain organ (YES in S1), the control section31receives, from a user via the input section34, organ information that identifies the organ (e.g., the name of the organ, the number assigned to the organ) (S2). The organ is a group of tissue having a certain function, such as lung, stomach, muscle, brain, or the like. Pieces of organ information about various types of organs, and reference wavelengths and discrimination wavelengths for use in identifying tissue constituting the organs, are associated with each other and stored in the storage section33.

Upon receipt of the organ information, the light source control section41of the control section31acquires, from the storage section33, a reference wavelength and a discrimination wavelength associated with the organ information (S3). The measurement position adjusting section46adjusts the position of the sample stage20, and thereby sets, to an initial position, the position to be irradiated with light of the reference wavelength and light of the discrimination wavelength (S4). Note that the adjustment of the position of the sample stage20(position on the sample S which position is irradiated with laser light100) can be carried out while the user is checking, via the display section32, an image captured by the image capturing section21. Note that the laser light100whose wavelength is within the foregoing range is invisible to the eye; therefore, it is preferable to provide a light source that emits visible light during the position adjustment.

The light source control section41controls the light source10to oscillate reference inspection light (having the reference wavelength associated with the organ information) and discrimination inspection light (having the discrimination wavelength associated with the organ information) (S5: applying step). In the following description, the reference inspection light and the discrimination inspection light are each referred to as laser light100. Part of the oscillated laser light100is detected at the monitor light detector16, and the rest of the oscillated laser light100passes through the sample S and then is detected at the light detector18.

The absorbance calculating section42recognizes signals outputted from the monitor light detector16and the light detector18, and thereby calculates the absorbance of each laser light100by the sample S (discrimination absorbance and reference absorbance) (S6: acquiring step).

The light source control section41and the absorbance calculating section42repeat steps S5and S6until the application of all types of laser light100of all the to-be-applied wavelengths is done (S7). Upon completion of the application of all types of laser light100and the measurement of absorbances (YES in S7), the absorbance ratio calculating section43calculates the ratio of the discrimination absorbance to the reference absorbance (S8: calculating step).

The identification information generating section45determines within which of a plurality of numerical ranges preset for the to-be-inspected organ the absorbance ratio calculated by the absorbance ratio calculating section43falls, and thereby determines whether or not the biological tissue in the sample S contains a tumor (S9).

FIG.6is a chart showing absorbance spectra for mammary tissue.FIG.6shows spectra of normal tissue, adenoma, fibroadenoma, and cancer tissue. The range represented by arrow83(9.80 μm to 10.60 μm), and also the ranges of from 8.05 μm to 8.15 μm, from 8.22 μm to 8.62 μm, from 8.71 μm to 8.85 μm, and from 8.88 μm to 10.6 μm, are the ranges of values that the discrimination wavelength can take. In these ranges, the absorbance differs among normal tissue, adenoma, fibroadenoma, and cancer tissue. Therefore, in a case where the organ is a mammary gland, for example, light of a wavelength of 9.75 μm can be used as a reference wavelength, and light of a wavelength of 10.05 μm can be used as a discrimination wavelength.

The range of values that the ratio of discrimination absorbance to reference absorbance (absorbance ratio) can take is preset for each of the following: normal tissue; adenoma; fibroadenoma; and cancer tissue. Such four numerical ranges are stored in the storage section33.

In a case where the absorbance ratio calculated by the absorbance ratio calculating section43falls within a numerical range that is associated with any of the following: adenoma; fibroadenoma; and cancer tissue, the identification information generating section45determines that the biological tissue contains a tumor (YES in S9ofFIG.5). The identification information generating section45further determines within which of the numerical ranges associated with adenoma, fibroadenoma, and cancer tissue the absorbance ratio calculated by the absorbance ratio calculating section43falls, and thereby determines whether the tumor is malignant (the tumor is cancer tissue) or benign (S10). The identification information generating section45may further determine whether the tumor is adenoma or fibroadenoma.

Note that the identification information generating section45may carry out steps S9and S10as a single step and thereby determine whether the biological tissue is normal tissue, adenoma, fibroadenoma, or cancer tissue in one step. Alternatively, the following arrangement may be employed: normal tissue, adenoma, and fibroadenoma are treated as tissue which is not cancer tissue; and the identification information generating section45only determines whether or not the sample S contains cancer tissue. Alternatively, the following arrangement may be employed: adenoma, fibroadenoma, and cancer tissue are treated as tumor tissue; and the identification information generating section45only determines whether or not the sample S contains tumor tissue.

Upon completion of the absorbance measurement and determination at the initially set measurement position, the measurement position adjusting section46causes the sample stage20to move and changes the measurement position (S11, S12).

Upon completion of the absorbance measurement and determination at every measurement position (YES in S11), the identification information generating section45generates identification information indicative of the type of the biological tissue, and outputs the identification information to the display section32(S13: outputting step).

On the contrary, in a case where it is unknown from which organ the biological tissue in the sample S is derived (NO in S1), steps S21to S27(organ determining step) are carried out. Specifically, the organ determining section44compares an absorbance spectrum of the biological tissue in the sample S with each of absorbance spectra (templates) of a plurality of types of organs pre-stored in the storage section33, and thereby determines from which organ the biological tissue in the sample S is derived. Note that the invention relating to steps S21to S27can be regarded as an invention independent of the invention relating to steps S2to S13.

FIG.7is a chart showing an example of templates for use in determining from which organ the biological tissue is derived.FIG.7shows smoothed versions of absorbance spectra of (1) normal tissue of lung, (2) cancer tissue of lung, (3) normal tissue of bone, (4) normal tissue of muscle, and (5) osteosarcoma. These templates, and data indicative of wavelength ranges of the respective templates, are pre-stored in the storage section33.

In the organ determining step, first, the light source control section41recognizes, from the storage section33, a wavelength range corresponding to all the templates (in the example shown inFIG.7, the range of 8.05 μm to 10.05 μm) (S21inFIG.5). Then, the position to be measured is set in a similar manner to S4(S22).

The light source control section41controls the light source10to set the oscillation wavelength of the light source10to one of the wavelengths in the wavelength range corresponding to a first template (S23).

The absorbance calculating section42calculates an absorbance by recognizing output signals from the monitor light detector16and the light detector18(S24). The wavelength set in S23is one of many wavelengths in the wavelength ranges corresponding to the respective templates. The absorbance measurement is carried out on each of these many wavelengths (S25). With this, an absorbance spectrum that can be compared with the templates is obtained. In order to efficiently obtain an absorbance spectrum in such a broad range, it is preferable to use, as the light source10, a light source including a quantum-cascade laser whose oscillation wavelength is adjustable in a mid-infrared region or a light source including an OPO (optical parametric oscillator)12.

The organ determining section44compares the absorbance spectrum obtained by the above-described measurement with each of the templates, and finds the template which is least different from the absorbance spectrum (S26). Any of known techniques can be used to carry out matching between the measured absorbance spectrum and templates. Then, the organ determining section44outputs, to the light source control section41and the identification information generating section45, organ information indicative of the organ corresponding to the found template (S26). The flow of the subsequent steps is the same as the flow of the foregoing steps S5to S13.

The organ determining section44does not necessarily need to output a single-meaning determination result. The organ determining section44may output, for example, organ information indicative of a plurality of candidate organs whose difference from the measured absorbance spectrum falls within a predetermined range.

The contrast of the absorbance may vary depending on conditions in which the measurement is carried out or the conditions (such as thickness) of the sample S. To address this, in a case of carrying out the matching, the spectral form may be corrected. For example, the measured absorbance spectrum may be corrected so that the difference between the maximum value and the minimum value of the measured absorbance spectrum is equal to the difference between the maximum value and the minimum value of a template.

As such, the presence of the organ determining section44makes it possible, even in cases of an unknown sample S, to identify biological tissue contained in the sample S. Furthermore, even in a case where cancer tissue derived from second tissue is present in first tissue, it is possible to appropriately identify such tissue.

Note that the organ determining section44may carry out organ determination by comparing (i) an absorbance spectrum indicated by light reflected from the biological tissue in the sample S and (ii) absorbance spectra pre-stored in the storage section33.

The organ determining section44may carry out organ determination with use of a transmittance spectrum indicated by light transmitted through the biological tissue in the sample S or a reflectance spectrum indicated by light reflected from the biological tissue in the sample S, instead of the foregoing absorbance spectrum. In this case, it is only necessary that a template(s) of a transmittance spectrum(spectra) be stored in the storage section33when transmittance is used or that a template(s) of a reflectance spectrum(spectra) be stored in the storage section33when reflectance is used.

The organ determining section44may carry out organ determination on a single position on the sample S or may carry out organ determination on a plurality of positions on the sample S. Furthermore, the organ determining section44and the identification information generating section45may carry out determination on the same position.

The organ determining section44may determine which type or state is a candidate for the type or state of the biological tissue, by comparing (i) the measured absorbance spectrum and (ii) pre-stored absorbance spectra for a plurality of types of tissue in a single organ. For example, the following arrangement may be employed: the organ determining section44provisionally determines whether the biological tissue in the sample S is normal tissue of lung or cancer tissue of lung like the example shown inFIG.7; and the identification information generating section45makes a final identification with use of the absorbance ratio. Furthermore, in a case of the intestinal tract, the organ determining section44may determine which of a plurality of types of tissue in the intestinal tract, e.g., epithelial tissue (mucus membrane), connective tissue, muscular tissue and the like, is a candidate for the biological tissue. That is, the organ determining section44determines which type or state is a candidate for the type or state of the to-be-inspected biological tissue. In such cases, in S27inFIG.5, the organ determining section44outputs information indicative of the candidate to the light source control section41and the identification information generating section45. The storage section33pre-stores therein the candidate, a reference wavelength, a discrimination wavelength, and the foregoing plurality of numerical ranges for identification.

In the above-described flow, the identification information generating section45acquires, from the user or the organ determining section44, the organ information indicating from which organ the biological tissue in the sample S is derived, and carries out the determination with use of the plurality of numerical ranges for the organ indicated by the organ information. Note, however, that the identification information generating section45may determine from which organ the biological tissue in the sample S is derived by determining within which of a plurality of preset numerical ranges the absorbance ratio falls. In this case, the organ determining section44is not essential.

(Example of how Identification Information is Displayed)

(a) ofFIG.8shows an example of an image of a sample S. (b) ofFIG.8shows an example of an image in a case where identification information generated by the identification information generating section45is displayed on the display section32. In the image of the biological tissue shown in (a) ofFIG.8, cancer tissue90is present. In the example shown in (b) ofFIG.8, the biological tissue identification system1divides the biological tissue into segments91each having a size of 500 μm×500 μm, and measures the absorbance on a per-segment-91basis. In S12ofFIG.5, the measurement position adjusting section46moves the position of the sample stage20so that all the segments91are measured for absorbance.

As the size of each segment91decreases, the accuracy of tissue identification increases. Therefore, each segment91preferably has a size of about 10 μm×10 μm.

(Case where a Plurality of Reference Wavelengths are Used and/or a Plurality of Discrimination Wavelengths are Used)

In a case where (i) a plurality of reference wavelengths and a discrimination wavelength are used, (ii) a reference wavelength and a plurality of discrimination wavelengths are used, or (iii) a plurality of reference wavelengths and a plurality of discrimination wavelengths are used, the absorbance calculating section42calculates a plurality of absorbance ratios and the identification information generating section45determines within which of predetermined numerical ranges each absorbance ratio falls.

Table 1 shows specific examples of a threshold for use for each combination of (i) the reference wavelength A (8.74 μm) or the reference wavelength B (9.73 μm) in the example shown inFIG.1and (ii) the discrimination wavelength A (8.28 μm) or the discrimination wavelength B (9.26 μm) in the example shown inFIG.1. The threshold is the value at the border between the range of absorbance ratios for normal tissue and the range of absorbance ratios for cancer tissue.

For example, in a case where the reference wavelength A and the discrimination wavelength B are used, the identification information generating section45determines that the biological tissue is cancer tissue if the absorbance ratio calculated by the absorbance ratio calculating section43is smaller than 0.9860.

In a case where the identification results based on the absorbance ratios (e.g., whether the biological tissue is normal tissue or cancer tissue) are different from each other, the identification information generating section45may output the identification result “cancer tissue” unless all the identification results are “normal tissue” or may output, as identification information, a value indicative of the ratio between the number of the identification results “normal tissue” and the number of the identification results “cancer tissue”.

Alternatively, the identification information generating section45may calculate a score indicative of the degree of certainty of the identification result obtained based on each absorbance ratio. The score can be, for example, a value indicative of how far the measured absorbance ratio is from the border between numerical ranges (threshold). The identification information generating section45may employ an identification result which is considered more reliable. For example, the identification information generating section45may employ an identification result which is based on an absorbance ratio with a higher score.

FIG.9is a chart showing absorbance spectra of normal tissue and cancer tissue (histiocytic sarcoma) in liver tissue. In the example shown inFIG.9, a reference wavelength is 9.75 μm, and a discrimination wavelength range is 9.33 μm to 9.64 μm.FIG.10is a chart showing absorbance spectra of cancer tissue (hepatocellular cancer) and lymphocyte in the liver. In the example shown inFIG.10, a reference wavelength is 9.75 μm, and discrimination wavelength ranges are 8.05 μm to 8.40 μm and 8.85 μm to 9.56 μm.FIG.11is a chart showing absorbance spectra of normal tissue of muscle, normal tissue of bone, and cancer tissue (osteosarcoma). In the example shown inFIG.11, a reference wavelength is 9.77 μm, and a discrimination wavelength range is 8.05 μm to 10.5 μm.FIG.12is a chart showing absorbance spectra of normal tissue and cancer tissue (medulloblastoma) in the cerebellum. In the example shown inFIG.12, a reference wavelength is 9.71 μm, and a discrimination wavelength range is 8.05 μm to 10.5 μm.FIG.13is a chart showing absorbance spectra of normal tissue and cancer tissue (malignant lymphoma) in the liver. In the example shown inFIG.13, a reference wavelength is 9.75 μm, and discrimination wavelength ranges are 9.07 μm to 9.77 μm and 9.82 μm to 10.8 μm.FIG.14is a chart showing absorbance spectra of normal tissue and cancer tissue (rhabdomyosarcoma) of muscle. In the example shown inFIG.14, a reference wavelength is 8.75 μm, and discrimination wavelengths ranges are 8.20 μm to 8.66 μm and 8.91 μm to 11.0 μm.FIG.15is a chart showing absorbance spectra of normal tissue and cancer tissue (histiocytic sarcoma) in the spleen. In the example shown inFIG.15, a reference wavelength is 9.76 μm, and discrimination wavelength ranges are 8.05 μm to 8.39 μm, 8.70 μm to 9.58 μm, and 9.87 μm to 10.9 μm.

It is apparent from these results that, for every organ, the absorbance spectrum differs significantly depending on the type or state of biological tissue, in the discrimination wavelength range represented by arrow83. It is possible to identify the type or state of the biological tissue by setting a reference wavelength, a discrimination wavelength, and the range of values that the absorbance ratio can take according to the type of organ or according to the purpose of identification. The reference wavelength, the discrimination wavelength, and the range of absorbance ratios can be set by: acquiring absorbance spectra of to-be-inspected biological tissue of various types; and comparing the acquired absorbance spectra.

The following description will discuss another embodiment of the present invention. For convenience of description, members having functions identical to those described in Embodiment 1 are assigned identical referential numerals, and their descriptions are omitted here.

FIG.16illustrates a configuration of a biological tissue identification system2in accordance with Embodiment 2. According to the biological tissue identification system2, the absorbance calculating section42calculates an absorbance indicated by reference inspection light reflected from biological tissue and an absorbance indicated by discrimination inspection light reflected from the biological tissue. The algorithm of tissue identification is the same as that of the biological tissue identification system1. The control section31may calculate the ratio of a reflectance indicated by discrimination inspection light reflected from the biological tissue to a reflectance indicated by reference inspection light reflected from the biological tissue, instead of the absorbance ratio.

In the biological tissue identification system2, one of the two portions of laser light100split by the beam splitter15is applied to the sample S fixed on the sample stage20, and a reflected portion of the laser light100reflected from the sample S (such a reflected portion is “reflected light100B”) is detected by the light detector18. Also in such a case in which reflected light is used, it is possible to appropriately carry out identification of biological tissue.

The following description will discuss a further embodiment of the present invention. (a) ofFIG.17is a cross-sectional view illustrating a configuration of an endoscope system3which is applicable to the biological tissue identification system1or the biological tissue identification system2. As illustrated in (a) ofFIG.17, the endoscope system3applies reference inspection light and discrimination inspection light to biological tissue and receives reflected light from the biological tissue.

The endoscope system3includes: a measuring head50for use near a living body L; a light source (first light source)10; and an illuminating light source (second light source)70. The illuminating light source70is a light source which emits visible light (illuminating light200) for optical observation of a to-be-measured area of the living body L through an image capturing section21.

The body (i.e., tube60) of the measuring head50contains therein a light detector (first light receiving section)18, the image capturing section (second light receiving section)21, and end portions of an inspection optical fiber (first optical fiber)51and an illuminating optical fiber (second optical fiber)54, which are arranged in the order named in the direction from the tip of the tube60. The inspection optical fiber51is an optical fiber which guides laser light100emitted from the light source10. The laser light100, after propagating through the inspection optical fiber51, is applied to the living body L through a condenser lens17provided on a side wall of the tube60. The illuminating optical fiber54is an optical fiber which guides illuminating light200emitted from the illuminating light source70. The illuminating optical fiber54is arranged coaxial with the inspection optical fiber51, and covers the outer surface of the inspection optical fiber51. The illuminating light200, after propagating through the illuminating optical fiber54, is applied to the living body L through the condenser lens17. The illuminating light200does not need to be laser light, and the illuminating optical fiber54does not need to be as high in propagation characteristics as the inspection optical fiber51.

The image capturing section21is constituted by an image pickup device211and an objective lens212provided on the side wall of the tube60. A reflected portion of the illuminating light reflected from the to-be-measured area of the living body L is received by the image pickup device211through the objective lens212, and thereby an image of the to-be-measured area is captured. A signal outputted from the image pickup device211is transmitted to the display section32, which allows a user to position the measuring head50while viewing a screen of the display section32.

The light detector18receives reflected light (diffused reflected light)100B, which is a reflected portion of the laser light100, from the living body L. The reflected light100B is light that penetrated into the biological tissue, was reflected by the biological tissue during the penetration, and thereby traveled out of the biological tissue. The reflected light100B enters the light detector18through an objective lens52on the side wall of the tube60and through a light-receiving optical fiber53. The magnification of the objective lens52is different from that of the condenser lens17. A signal outputted from the light detector18is transmitted to the control section31of the biological tissue identification system1or of the biological tissue identification system2. The light detector18can be a small light detector, such as a pyroelectric infrared detector.

(b) ofFIG.17illustrates the side wall of the tube60. As illustrated in (b) ofFIG.17, the objective lens52corresponding to the light detector18, the objective lens212of the image pickup device211, and the condenser lens17located at the exit-side end of the inspection optical fiber51(and illuminating optical fiber54) are arranged close to each other in the order named in the direction from the tip of the tube60. Such a manner of arrangement makes it possible to capture an image of the area irradiated with the laser light100and also possible to receive a reflected portion of the laser light100reflected from the living body L.

Note, however, that the manner in which the light detector18, the image pickup device211, the inspection optical fiber51, and the illuminating optical fiber54are arranged in the tube60is not limited to that described above. For example, the relative positons of (i) the inspection optical fiber51and the illuminating optical fiber54and (ii) the light detector18can be switched.

With use of the endoscope system3including the measuring head50, it is possible to apply laser light100to an intended area of the living body L and noninvasively identify biological tissue utilizing a reflected portion of the laser light100reflected from the living body L. The measuring head50is flexible; therefore, with use of the measuring head50which is small in size, it is possible to insert the measuring head50into various types of organs of the living body, and thus possible to identify tissue in those organs.

Furthermore, since the inspection optical fiber51and the illuminating optical fiber54are arranged coaxially with each other, it is possible to unfailingly apply illuminating light to an area irradiated with inspection light (i.e., area to be measured). This ensures that the user can see the area to be measured.

The following description will discuss still a further embodiment of the present invention. A biological tissue identification system1ain accordance with Embodiment 4 is different from the biological tissue identification system1in that the biological tissue identification system1aincludes an objective mirror (not illustrated, also called “reflective objective lens”) instead of the condenser lens17. The objective mirror includes a reflector therein, and focuses laser light100by reflecting the laser light100at the reflector. The use of such an objective mirror makes it possible to reduce the diameter of the laser light100.

In the biological tissue identification system1a, the laser light100focused by the objective mirror is applied to the sample S (applying step), and transmitted light100A (transmitted portion of the laser light100transmitted through the sample S) or reflected light100B (reflected portion of the laser light100reflected from the sample S) is received by the light detector18(receiving step).

The objective mirror is, for example, an objective mirror of Schwarzschild type which is constituted by reflecting surfaces of metal coatings. The NA of the objective mirror is, for example, 0.3, and the focal length of the objective mirror is, for example, 13.3 mm.

The biological tissue identification system1aincludes the objective mirror, and therefore is capable of further reducing the beam spot size compared to a case where the condenser lens17is used. With this, the irradiated region of the sample S irradiated with the laser light100decreases in size, that is, the segments91decrease in size. This makes it possible to increase the number of segments91per unit area. For example, in a case where the biological tissue identification system1is used, the segments91each have a size of 500 μm×500 μm, whereas, in a case where the biological tissue identification system1ais used, segments91each having a size of about 70 μm×70 μm can be achieved. Thus, the use of the biological tissue identification system1amakes it possible to obtain a more detailed (higher-resolution) identification result.

The following description discusses an example in which a high-resolution identification result was obtained, with reference toFIG.18. In the example shown inFIG.18, liver tissue is used as the sample S. (a) ofFIG.18shows identification information outputted by the biological tissue identification system1. (b) ofFIG.18is an image of the liver tissue which is to be identified. (c) ofFIG.18is the image of the liver tissue on which another image (i.e., identification information provided by the biological tissue identification system1a) is superimposed. (d) ofFIG.18is an enlarged view of a part of the image of the liver tissue enclosed by solid line in (c) ofFIG.18.

Note here that (a) ofFIG.18shows identification results for the part enclosed by solid line in (b) ofFIG.18, and (c) ofFIG.18shows identification results for the part enclosed by dashed line in (b) ofFIG.18. The part enclosed by dashed line in (d) ofFIG.18is an area which has been pathologically diagnosed as cancer tissue (area infiltrated with malignant lymphoma cells). Note that the identification results shown in (a) and (c) ofFIG.18are those obtained with use of the same sample, and the images shown in (b) and (d) ofFIG.18are those obtained by staining a sample taken from the vicinity of the above-mentioned sample.

As shown in (a) to (c) ofFIG.18, in a case where the biological tissue identification system1ais used, the segments91are smaller in size and therefore larger in number than in the case where the biological tissue identification system1is used. Thus, a detailed identification result was obtained. Furthermore, a comparison between (c) ofFIG.18and (d) ofFIG.18shows that the shape of the area which has been determined by the identification information generating section45as being highly likely to be “cancer tissue” and the shape of the area which has been diagnosed as cancer tissue based on a histopathological image are substantially the same. That is, the biological tissue identification system1ahas more improved resolution than the biological tissue identification system1, and is capable of obtaining a highly accurate identification result. With this, the biological tissue identification system1ais capable of, even if cancer tissue is very small, accurately identifying the position and shape of the cancer tissue.

The identification information generating section45may output, to the display section32, the results of tissue determination as an image so that, as shown in (c) ofFIG.18, each segment91is displayed in a color that corresponds to the result of tissue determination on that segment91and thereby the results of tissue determination are visually perceivable as an image of the tissue.

An object of the invention in accordance with Embodiment 4 is to increase the accuracy of measurement of the transmittance, reflectance, or absorbance of light applied to biological tissue. This is described below.

FIG.19illustrates the waveforms of pulses obtained during oscillation of laser light100. The light source10of the biological tissue identification system1aoscillates pulsed laser light100. The inventors measured the waveforms of pulses when the light source10oscillated the laser light100, with use of a photodetector. Specifically, the inventors used the photodetector to convert the laser light100emitted by the light source10into electrical signal, and observed the electrical signal with an oscilloscope.

As illustrated inFIG.19, the laser light100oscillated by the light source10contains a main pulse300and a subpulse301. The main pulse300is a main component of the laser light100. The subpulse301is an inevitably generated pulse accompanying the main pulse300.

The same measurement was carried out a plurality of times, and it was found that the intensity of the subpulse301varies from one wavelength to another or changes each time the measurement is carried out. Furthermore, when an absorbance was calculated in the biological tissue identification system1, temporal integration was carried out on laser light including all the main pulses300and subpulses301. These demonstrate that the subpulse301can affect the result of measurement of absorbance (transmittance or reflectance) as noise.

In view of above, in order to reduce the effect of the subpulse301on the measurement result and improve the accuracy of measurement, the inventors have achieved a method in which (i) transmitted light100A (or reflected light100B) derived from the main pulse300is detected by the light detector18and (ii) transmitted light100A (or reflected light100B) derived from the subpulse301is not detected by the light detector18.

Specifically, the following describes an inspection method in accordance with Embodiment 4. The inventors set a time gate width304, i.e., the time for which the light detector18is allowed to detect only the transmitted light100A (or the reflected light100B), and limited the time for which the light detector18is allowed to receive light. The time gate width304is set such that the time gate width304is equal to or longer than a pulse width302of the main pulse300. With this, the biological tissue identification system1acalculates an absorbance by carrying out temporal integration of only main pulses300.

For ensuring that the main pulse300in its entirety will be measured, the time gate width304is set such that the time gate width304contains not only the pulse width302but also times before and after the pulse width302(i.e., the times represented by arrows303inFIG.19). Each time represented by arrow303is preferably set such that the time does not contain the time during which the subpulse301is generated. Specifically, each of the times represented by arrows303inFIG.19need only be set to about 0% to 10% of the pulse width302, e.g., 3% of the pulse width302.

Note that the point in time at which the light source10oscillates the laser light100and the point in time at which the light detector18detects the transmitted light100A are not exactly the same. Therefore, the points in time at which the light detector18is allowed to receive light need only be set in consideration of the above-mentioned difference between points in time.

Also note that Embodiment 4 is not intended for completely avoiding the detection of the subpulse301. The subpulse301may be detected, provided that tissue identification is not affected. That is, in Embodiment 4, it is only necessary that the time gate width304be set so that at least part of the subpulse301is not detected by the light detector18.

Furthermore, in a case where the pulse width302is the same among all wavelengths for use in measurements, the measurements may be carried out with use of a fixed time gate width304for all those wavelengths. However, in a case where the pulse width302differs from one wavelength to another, the time gate width304is preferably changed on a per-wavelength basis as necessary.

FIG.20is a functional block diagram illustrating a configuration of a control section31aof the biological tissue identification system1ain accordance with Embodiment 4. Except for the control section31a, the biological tissue identification system1ais the same in configuration as the biological tissue identification system1.

As illustrated inFIG.20, the control section31aof the computer30controls the light detector18to detect the transmitted light100A or the reflected light100B only in the duration of the foregoing time gate width304. With this, the biological tissue identification system1ais capable of obtaining an identification result less affected by the subpulse301, i.e., noise. That is, it is possible to further improve the accuracy of tissue identification.

The configuration discussed in Embodiment 4 is one in which the objective mirror and the control section31aare employed in the configuration of the biological tissue identification system1. Such a configuration is also applicable to Embodiments 2 and 3, and such Embodiments 2 and 3 also provide a similar effect.

(Effect of Biological Tissue Identification System1a)

The biological tissue identification system1and the biological tissue identification system1awere used to measure absorbance spectra of normal liver and an area infiltrated with malignant lymphoma cells in liver tissue. Note that, in this measurement, the pulse width302for all wavelengths for use in the measurement was 557 ns, and the time gate width304was fixed at 590 ns (the sum of the pulse width302and 3% of the pulse width302at each edge of the pulse). Each tissue was subjected to the measurement a plurality of times.FIG.21shows charts showing the absorbance spectra of normal liver and an area infiltrated with malignant lymphoma cells in liver tissue. (a) ofFIG.21shows absorbance spectra obtained with use of the biological tissue identification system1, and (b) ofFIG.21shows absorbance spectra obtained with use of the biological tissue identification system1a. Note that the absorbance spectra shown in (a) and (b) ofFIG.21were obtained by measuring the same sample.

As shown in (b) ofFIG.21, the difference between the normal liver and the area infiltrated with malignant lymphoma cells is more apparent in the results of measurement carried out by the biological tissue identification system1athan in the results of measurement carried out by the biological tissue identification system1shown in (a) ofFIG.21. That is, it was confirmed that, in the biological tissue identification system1a, the resolution is improved by the presence of the objective mirror, the effect of the subpulse301is reduced by setting the time gate width304, and therefore the accuracy of measurement of absorbance spectra is improved.

In particular, as shown in (a) ofFIG.21, in the case of measurement using the biological tissue identification system1, for example, when the measurement was carried out with use of light of a wavelength of 9.83 μm, the absorbance of normal tissue varied greatly each time it was measured, and the result of tissue identification was indefinite. Furthermore, when the measurement was carried out with use of light of a wavelength 9.07 μm, the difference in absorbance between the normal tissue and the area infiltrated with malignant lymphoma cells was small. In contrast, as shown in (b) ofFIG.21, in the case of measurement using the biological tissue identification system1a, when the measurement was carried out with use of light of a wavelength of 9.83 μm, the variation in absorbance of the normal tissue among measurements was small. Furthermore, when the measurement was carried out with use of light of a wavelength of 9.07 μm, the difference between the normal liver and the area infiltrated with malignant lymphoma cells was clearly recognizable.

Examples of measurements which were carried out using the biological tissue identification system1aare discussed below with reference toFIGS.22to29. Note that each tissue was subjected to measurement a plurality of times.FIG.22is a chart showing absorbance spectra of a plurality of different types of tissue and cancer tissue. In the example shown inFIG.22, the measurement was carried out on bone marrow, rhabdomyosarcoma (cancer tissue), muscle, and bone, and a reference wavelength is 8.84 μm and a discrimination wavelength range is 8.87 μm to 9.02 μm.FIG.23is a chart showing absorbance spectra of normal tissue, cancer tissue, and lymphocyte in liver tissue. In the example shown inFIG.23, a reference wavelength is 9.75 μm and a discrimination wavelength range is 9.10 μm to 9.55 μm.FIG.24is a chart showing absorbance spectra of normal tissue, primary lung cancer tissue, and a lesion of pulmonary metastasis of liver cancer in lung tissue. In the example shown inFIG.24, a reference wavelength is 9.70 μm and a discrimination wavelength range is 9.75 μm to 10.00 μm.

FIG.25is a chart showing absorbance spectra of normal tissue and a cardiac infarct area in heart tissue. In the example shown inFIG.25, a reference wavelength is 8.76 μm and discrimination wavelength ranges are 9.18 μm to 9.71 μm and 9.84 μm to 11.00 μm.FIG.26is a chart showing absorbance spectra of normal tissue and tissue of fatty liver in liver tissue. In the example shown inFIG.26, a reference wavelength is 9.75 μm and a discrimination wavelength range is 8.05 μm to 9.18 μm.FIG.27is a chart showing absorbance spectra of normal tissue and tissue of liver cirrhosis in liver tissue. In the example shown inFIG.27, a reference wavelength is 9.75 μm and discrimination wavelength ranges are 8.61 μm to 9.00 μm and 9.05 μm to 9.26 μm.

FIG.28is a chart showing absorbance spectra of normal tissue, radiation-induced cancer tissue, and spontaneous cancer tissue in cerebellar tissue (medulloblastoma). In the example shown inFIG.28, a reference wavelength is 9.71 μm and discrimination wavelength ranges are 8.80 μm to 9.34 μm and 9.89 μm to 10.25 μm.FIG.29is a chart showing absorbance spectra of a normal renal tubule and a glomerulus with amyloid deposition in kidney tissue. In the example shown inFIG.29, a reference wavelength is 9.73 μm, and a discrimination wavelength range is 8.88 μm to 9.14 μm.

In each of the results shown inFIGS.22to29, it is apparent that the absorbance spectrum differs significantly depending on the type or state of biological tissue, in the discrimination wavelength ranges represented by arrows83,83A, and83B. The results shown inFIG.22indicate that it is possible to identify cancer tissue in a plurality of types of tissue.

The absorbance spectra shown in the example of inFIG.23are those obtained using samples whose border between normal tissue, cancer tissue, and lymphocyte is unclear in histopathological images. The results shown inFIG.23indicate that, even in a case where the border between different types of tissue is unclear, it is possible to identify each tissue in the discrimination wavelength range represented by arrow83.

Furthermore, the results shown inFIG.24indicate that, in the discrimination wavelength range represented by arrow83, it is possible to identify normal tissue and cancer tissue and also identify from which tissue the cancer tissue is derived. For example, it is possible to identify whether the cancer tissue is metastatic cancer tissue or primary cancer tissue.

Furthermore, the results shown inFIG.25indicate that it is possible to identify normal tissue and a cardiac infarct area in the discrimination wavelength ranges represented by arrows83A and83B. The results indicate that, in particular, in a case where the measurement is carried out with use of light of a wavelength of 9.62 μm, it is possible to precisely identify the cardiac infarct area.

The results shown inFIGS.26and27indicate that it is possible to identify normal tissue and tissue of fatty liver in the discrimination wavelength range represented by arrow83inFIG.26and possible to identify normal tissue and tissue of liver cirrhosis in the discrimination wavelength ranges represented by arrows83A and83B inFIG.27. In addition, as described earlier, it is also possible to identify normal tissue and cancer tissue in liver tissue.

With regard to liver tissue, normal tissue becomes fatty liver when lipid droplets accumulate in hepatocytes, whereas the normal tissue becomes liver cirrhosis when fibrosis occurs due to collagen depositions. Furthermore, liver cancer may originate from the liver cirrhosis. In Embodiment 4, it is possible to identify in which stage the carcinogenesis process in the liver tissue is.

The results shown inFIG.28indicate that, in the discrimination wavelength ranges represented by arrows83A and83B, it is possible to identify normal tissue and cancer tissue and also identify whether the cancer tissue is spontaneous cancer tissue or radiation-induced cancer tissue. It has been difficult to distinguish between radiation-induced cancer tissue and spontaneous cancer tissue in a histopathological image; however, in Embodiment 4, it is possible to identify such types of cancer tissue.

The results shown inFIG.29indicate that, in the discrimination wavelength range represented by arrow83, it is possible to identify a normal renal tubule and a glomerulus amyloid deposition. The glomerulus with amyloid with deposition is a cause of proteinuria and nephrotic syndrome, and its progression may cause chronic renal failure. Thus, in Embodiment 4, it is possible to identify tissue at risk of chronic renal failure before the chronic renal failure occurs, i.e., it is possible to identify tissue in which there is an abnormality. It is considered that it is also possible to identify whether there is amyloid deposition or not before the onset of a symptom (in the early stage) similarly in every organ of the body such as brain, heart, alimentary tract, liver, peripheral nerve, tongue, thyroid, and skin.

Software Implementation Example

Control blocks of the control section31(particularly, the absorbance ratio calculating section43, the organ determining section44, and the identification information generating section45) can be realized by a logic circuit (hardware) provided in an integrated circuit (IC chip) or the like or can be alternatively realized by software.

In the latter case, the control section31is realized as a computer that executes instructions of a tissue identification program that is software realizing the foregoing functions. The control section31, for example, includes at least one processor, and is communicably connected to the storage section33which is a computer-readable storage medium storing the program. An object of the present invention can be achieved by the processor of the control section31reading and executing the program stored in the storage medium.

Examples of the processor encompass a central processing unit (CPU). Examples of the storage medium encompass a “non-transitory tangible medium” such as a read only memory (ROM), a tape, a disk, a card, a semiconductor memory, and a programmable logic circuit. The computer may further include a random access memory (RAM) or the like in which the program is loaded. Further, the program may be made available to the computer via any transmission medium (such as a communication network and a broadcast wave) which allows the program to be transmitted. Note that an aspect of the present invention can also be achieved in the form of a computer data signal in which the program is embodied via electronic transmission and which is embedded in a carrier wave.

REFERENCE SIGNS LIST