1. Field of the Invention
This invention relates to a method and apparatus for displaying fluorescence information, wherein excitation light is irradiated to a region of interest in a living body, intrinsic fluorescence produced by an intrinsic dye in the living body is detected, and information in accordance with characteristics of the intrinsic fluorescence is displayed.
2. Description of the Related Art
There have heretofore been proposed fluorescence information displaying techniques utilizing characteristics such that, in cases where excitation light having wavelengths falling within an excitation wavelength range for an intrinsic dye in a living body is irradiated to the living body, an intensity of fluorescence produced by the intrinsic dye in the living body varies for normal tissues and diseased tissues. With the proposed fluorescence information displaying techniques, excitation light having predetermined wavelengths is irradiated to a region of interest in a living body, the fluorescence produced by an intrinsic dye in the living body is detected, and the location and the infiltration range of diseased tissues are displayed as a fluorescence image.
Ordinarily, when excitation light is irradiated to a region of interest in a living body, the fluorescence having a high intensity is produced by normal tissues, and the fluorescence having a low intensity is produced by diseased tissues. Therefore, by measurement of the fluorescence intensity, a judgment as to the state of a disease is capable of being made.
Basically, apparatuses for displaying fluorescence information comprise excitation light irradiating means for irradiating excitation light, which has wavelengths falling within an excitation wavelength range for an intrinsic dye in a living body, to the living body, imaging means for detecting fluorescence produced by the intrinsic dye in the living body and forming a fluorescence image of the living body, and image displaying means for receiving the output from the imaging means and displaying the fluorescence image. In many cases, the apparatuses for displaying fluorescence information take on the form built in endoscopes, which are inserted into the body cavities, colposcopes, operating microscopes, or the like.
However, the aforesaid apparatuses for displaying fluorescence information have the problems described below. Specifically, since a region in a living body has protrusions and recesses, the distance between the light source of the excitation light irradiating means and the region of interest in the living body is not uniform. Therefore, ordinarily, the irradiance of the excitation light at the living body portion, which is exposed to the excitation light, is non-uniform. The intensity of fluorescence is approximately in proportion to the irradiance of the excitation light, and the irradiance of the excitation light at the portion, which is exposed to the excitation light, is in inverse proportion to the square of the distance between the light source of the excitation light irradiating means and the portion, which is exposed to the excitation light. Accordingly, the problems occur in that diseased tissues, which are located close to the light source, produce the fluorescence having a higher intensity than the intensity of the fluorescence produced by normal tissues, which are located remote from the light source. The problems also occur in that the intensity of the fluorescence from normal tissues, which are located at a position inclined with respect to the excitation light, becomes markedly low. Thus if the irradiance of the excitation light is non-uniform, the intensity of the fluorescence will vary in accordance with the level of the irradiance of the excitation light, and therefore an error will often be made in the judgment of the state of a disease.
A fluorescence imaging technique has been proposed in, for example, xe2x80x9cFluorescence Imaging of Early Lung Cancer,xe2x80x9d Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Vol. 12, No. 3, 1990. With the proposed technique, the fluorescence, which is produced by an intrinsic dye in an region of interest in a living body when the region of interest is exposed to excitation light, is separated into an intensity of the green wavelength region (hereinbelow referred to as the xe2x80x9cgreen region intensity Gxe2x80x9d) and an intensity of the red wavelength region (hereinbelow referred to as the xe2x80x9cred region intensity Rxe2x80x9d). An image operation is then performed in accordance with division of the red region intensity R and the green region intensity G by each other, and the results of the division are displayed. The proposed technique utilizes the findings in that the spectrum of the fluorescence produced by normal tissues is different from the spectrum of the fluorescence produced by diseased tissues. Specifically, when the spectrum of the fluorescence, which is produced by the intrinsic dye at normal tissues in the living body, and the spectrum of the fluorescence, which is produced by the intrinsic dye at diseased tissues in the living body, are compared with each other, in particular, the intensity of the green region of the spectrum obtained from the diseased tissues is markedly lower than the intensity of the green region of the spectrum obtained from the normal tissues. Therefore, the degree of reduction in the intensity of the green region intensity G of the fluorescence, which is produced from the diseased tissues, as compared with the intensity of the green region intensity G of the fluorescence produced from the normal tissues, is markedly higher than the degree of reduction in the intensity of the red region intensity R of the fluorescence, which is produced from the diseased tissues, as compared with the intensity of the red region intensity R of the fluorescence produced from the normal tissues. Therefore, only the fluorescence from the diseased tissues can be specifically extracted by the division of R/G and can be displayed as an image.
Specifically, with the proposed technique, the term of the fluorescence intensity depending upon the distance between the excitation light source and the region of interest in the living body and the distance between the region of interest in the living body and the fluorescence receiving means is canceled, and information reflecting only the difference in fluorescence spectrum pattern is obtained.
However, heretofore, research has not been conducted sufficiently with respect to a combination of detection wavelengths, at which the difference between the pattern of a fluorescence spectrum obtained from normal tissues and the pattern of a fluorescence spectrum obtained from diseased tissues occurs markedly. Therefore, there have been the problems in that a desirable combination of detection wavelengths cannot be presented with numerical values.
The primary object of the present invention is to provide a method of displaying fluorescence information, wherein fluorescence components having two different wavelengths are extracted from fluorescence, the two different wavelengths having been specified with numerical values as an appropriate combination of detection wavelengths, at which a difference between a pattern of a fluorescence spectrum obtained from normal tissues and a pattern of a fluorescence spectrum obtained from diseased tissues occurs markedly, light intensities of the extracted fluorescence components are detected, and information in accordance with a ratio between the light intensities of the extracted fluorescence components is displayed with a high reliability.
Another object of the present invention is to provide a method of displaying fluorescence information, wherein fluorescence components having wavelengths falling within a certain wavelength region are extracted from fluorescence, the certain wavelength region having been specified with numerical values as an appropriate detection wavelength region, at which a difference between a fluorescence intensity of fluorescence produced from normal tissues and a fluorescence intensity of fluorescence produced from diseased tissues occurs markedly, a light intensity of the extracted fluorescence components is detected, and information in accordance with the detected light intensity is displayed with a high reliability.
The specific object of the present invention is to provide an apparatus for carrying out the method of displaying fluorescence information.
The present invention provides a first method of displaying fluorescence information, comprising the steps of:
i) irradiating excitation light to a measuring site in a living body, the excitation light causing the measuring site to produce fluorescence,
ii) detecting light intensity of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a predetermined wavelength region containing 480 nm,
iii) detecting light intensity of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a predetermined wavelength region containing either one of 630 nm and 700 nm, and
iv) displaying information in accordance with a ratio between the two detected light intensities.
The present invention also provides a first apparatus for displaying fluorescence information, comprising:
i) excitation light irradiating means for irradiating excitation light to a measuring site in a living body, the excitation light causing the measuring site to produce fluorescence,
ii) first fluorescence intensity detecting means for detecting light intensity of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a predetermined wavelength region containing 480 nm,
iii) second fluorescence intensity detecting means for detecting light intensity of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a predetermined wavelength region containing either one of 630 nm and 700 nm, and
iv) displaying means for displaying information in accordance with a ratio between the light intensity, which has been detected by the first fluorescence intensity detecting means, and the light intensity, which has been detected by the second fluorescence intensity detecting means.
The first apparatus for displaying fluorescence information in accordance with the present invention should preferably be modified such that the first fluorescence intensity detecting means comprises:
first wavelength selecting means for selecting the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the predetermined wavelength region containing 480 nm, and
first light intensity detecting means for detecting the light intensity of the fluorescence components having been selected by the first wavelength selecting means, and
the second fluorescence intensity detecting means comprises:
second wavelength selecting means for selecting the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the predetermined wavelength region containing either one of 630 nm and 700 nm, and
second light intensity detecting means for detecting the light intensity of the fluorescence components having been selected by the second wavelength selecting means.
Also, the first apparatus for displaying fluorescence information in accordance with the present invention should more preferably be modified such that the first wavelength selecting means selects the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the predetermined wavelength region of 480 nmxc2x1at most 70 nm, and
the second wavelength selecting means selects the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the predetermined wavelength region of either one of 630 nmxc2x1at most 70 nm and 700 nmxc2x1at most 70 nm.
Further, in the first apparatus for displaying fluorescence information in accordance with the present invention, the excitation light should preferably have wavelengths falling within the range of 380 nm to 420 nm, which range is apart from the characteristic peak light intensity of the fluorescence produced from normal tissues of the living body. Furthermore, in the first apparatus for displaying fluorescence information in accordance with the present invention, the excitation light irradiating means should preferably be a GaN type of semiconductor laser.
The first apparatus for displaying fluorescence information in accordance with the present invention may be constituted so as to two-dimensionally detect a fluorescence image. Alternatively, the first apparatus for displaying fluorescence information in accordance with the present invention may be constituted so as to detect the fluorescence intensity with respect to each point at a site in the living body.
Also, in the first apparatus for displaying fluorescence information in accordance with the present invention, by way of example, each of the first wavelength selecting means and the second wavelength selecting means may be constituted so as to extract the fluorescence components, which have wavelengths falling within the predetermined wavelength region, with a dichroic mirror, or the like. Alternatively, each of the first wavelength selecting means and the second wavelength selecting means may be constituted so as to extract the fluorescence components, which have wavelengths falling within the predetermined wavelength region, in a time division mode by changing over an optical filter, or the like. As another alternative, in cases where a fluorescence image is to be detected two-dimensionally, each of the first wavelength selecting means and the second wavelength selecting means may be constituted so as to extract the fluorescence components, which have wavelengths falling within the predetermined wavelength region, by utilizing-a mosaic filter formed by connecting optical filters with one another in a mosaic pattern.
Further, in the first apparatus for displaying fluorescence information in accordance with the present invention, the displaying means may employ one of various displaying techniques. For example, the displaying means may be constituted so as to display the ratio between the light intensity of the fluorescence components, which have wavelengths falling within the predetermined wavelength region containing 480 nm, and the light intensity of the fluorescence components, which have wavelengths falling within the predetermined wavelength region containing either one of 630 nm and 700 nm, on a monitor, with a printer, or the like. Alternatively, the displaying means may be constituted so as to alter the tint or the luminance of the displayed color in accordance with the ratio between the two light intensities.
The present invention further provides a second method of displaying fluorescence information, comprising the steps of:
i) irradiating excitation light to a measuring site in a living body, the excitation light causing the measuring site to produce fluorescence,
ii) detecting light intensity B of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a wavelength region of 480 nmxc2x1at most 70 nm and at least containing 450 nm to 480 nm, and
iii) displaying information in accordance with the light intensity B.
The present invention still further provides a third method of displaying fluorescence information, comprising the steps of:
i) irradiating excitation light to a measuring site in a living body, the excitation light causing the measuring site to produce fluorescence,
ii) detecting light intensity W of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within an entire measurement wavelength region,
iii) detecting at least one light intensity selected from among:
light intensity Bxe2x80x2 of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a wavelength region of 480 nmxc2x1at most 70 nm and at least containing 450 nm to 480 nm,
light intensity R1 of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a wavelength region of 630 nmxc2x1at most 70 nm and at least containing 600 nm to 630 nm, and
light intensity R2 of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a wavelength region of 700 nmxc2x1at most 70 nm and at least containing 700 nm to 710 nm, and
iv) displaying information in accordance with a ratio between the at least one selected light intensity and the light intensity W.
The present invention also provides a fourth method of displaying fluorescence information, comprising the steps of:
i) irradiating excitation light to a measuring site in a living body, the excitation light causing the measuring site to produce fluorescence,
ii) detecting light intensity B of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a wavelength region of 480 nmxc2x1at most 70 nm and at least containing 450 nm to 480 nm,
iii) detecting light intensity W of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within an entire measurement wavelength region,
iv) detecting at least one light intensity selected from among:
light intensity Bxe2x80x2 of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a wavelength region of 480 nmxc2x1at most 70 nm and at least containing 450 nm to 480 nm,
light intensity R1 of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a wavelength region of 630 nmxc2x1at most 70 nm and at least containing 600 nm to 630 nm, and
light intensity R2 of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a wavelength region of 700 nmxc2x1at most 70 nm and at least containing 700 nm to 710 nm, and
v) displaying information in accordance with the light intensity B and a ratio between the at least one light intensity, which is selected from among the light intensities Bxe2x80x2, R1, and R2, and the light intensity W.
In the third and fourth methods of displaying fluorescence information in accordance with the present invention, in cases where the light intensity Bxe2x80x2 is detected as the at least one light intensity, the light intensity Bxe2x80x2 may be the light intensity of the fluorescence components having wavelengths falling within the wavelength region identical with the wavelength region of the fluorescence components, whose light intensity is detected as the light intensity B. Alternatively, the light intensity Bxe2x80x2 may be the light intensity of the fluorescence components having wavelengths falling within the wavelength region different from the wavelength region of the fluorescence components, whose light intensity is detected as the light intensity B. In the former cases, instead of the light intensity Bxe2x80x2 being detected besides the light intensity B, the light intensity B may be employed as the light intensity Bxe2x80x2. The term xe2x80x9cdetecting light intensity Bxe2x80x2 xe2x80x9d as used herein also includes the cases where the light intensity B is employed as the light intensity Bxe2x80x2.
The present invention further provides a second apparatus for displaying fluorescence information, comprising:
i) excitation light irradiating means for irradiating excitation light to a measuring site in a living body, the excitation light causing the measuring site to produce fluorescence,
ii) first light intensity detecting means for detecting light intensity B of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a wavelength region of 480 nmxc2x1at most 70 nm and at least containing 450 nm to 480 nm, and
iii) fluorescence information displaying means for displaying information in accordance with the light intensity B having been detected by the first light intensity detecting means.
The present invention still further provides a third apparatus for displaying fluorescence information, comprising:
i) excitation light irradiating means for irradiating excitation light to a measuring site in a living body, the excitation light causing the measuring site to produce fluorescence,
ii) second light intensity detecting means for detecting light intensity W of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within an entire measurement wavelength region,
iii) at least one light intensity detecting means selected from among:
third light intensity detecting means for detecting light intensity Bxe2x80x2 of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a wavelength region of 480 nmxc2x1at most 70 nm and at least containing 450 nm to 480 nm,
fourth light intensity detecting means for detecting light intensity R1 of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a wavelength region of 630 nmxc2x1at most 70 nm and at least containing 600 nm to 630 nm, and
fifth light intensity detecting means for detecting light intensity R2 of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a wavelength region of 700 nmxc2x1at most 70 nm and at least containing 700 nm to 710 nm, and
iv) fluorescence information displaying means for displaying information in accordance with a ratio between the light intensity, which has been detected by the at least one selected light intensity detecting means, and the light intensity W.
The present invention also provides a fourth apparatus for displaying fluorescence information, comprising:
i) excitation light irradiating means for irradiating excitation light to a measuring site in a living body, the excitation light causing the measuring site to produce fluorescence,
ii) first light intensity detecting means for detecting light intensity B of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a wavelength region of 480 nmxc2x1at most 70 nm and at least containing 450 nm to 480 nm,
iii) second light intensity detecting means for detecting light intensity W of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within an entire measurement wavelength region,
iv) at least one light intensity detecting means selected from among:
third light intensity detecting means for detecting light intensity Bxe2x80x2 of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a wavelength region of 480 nmxc2x1at most 70 nm and at least containing 450 nm to 480 nm,
fourth light intensity detecting means for detecting light intensity R1 of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a wavelength region of 630 nmxc2x1at most 70 nm and at least containing 600 nm to 630 nm, and
fifth light intensity detecting means for detecting light intensity R2 of fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a wavelength region of 700 nmxc2x1at most 70 nm and at least containing 700 nm to 710 nm, and
v) fluorescence information displaying means for displaying information in accordance with the light intensity B and a ratio between the light intensity, which has been detected by the at least one selected light intensity detecting means, and the light intensity W.
In the third and fourth apparatuses for displaying fluorescence information in accordance with the present invention, in cases where the third light intensity detecting means is provided as the at least one light intensity detecting means, the third light intensity detecting means may be identical with the first light intensity detecting means. Alternatively, the third light intensity detecting means may be different from the first light intensity detecting means. In the former cases, instead of the third light intensity detecting means being provided besides the first light intensity detecting means, the first light intensity detecting means may be utilized as the third light intensity detecting means. The term xe2x80x9ccomprising third light intensity detecting meansxe2x80x9d as used herein also includes the cases where the first light intensity detecting means is utilized as the third light intensity detecting means.
The second, third, and fourth apparatuses for displaying fluorescence information in accordance with the present invention should preferably be modified such that the light intensity detecting means comprises an image sensor for two-dimensionally detecting the fluorescence produced by the measuring site and forming a fluorescence image, and wavelength selecting means for selecting the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a desired wavelength region.
Also, the second, third, and fourth apparatuses for displaying fluorescence information in accordance with the present invention may be modified such that the light intensity detecting means is provided with fluorescence acquiring means for acquiring the fluorescence, which is produced by a single point at a site in the living body.
Further, in the second, third, and fourth apparatuses for displaying fluorescence information in accordance with the present invention, the excitation light should preferably have wavelengths falling within the range of 380 nm to 420 nm, which range is apart from the characteristic peak light intensity of the fluorescence produced from normal tissues of the living body. Furthermore, in the second, third, and fourth apparatuses for displaying fluorescence information in accordance with the present invention, the excitation light irradiating means should preferably be a GaN type of semiconductor laser.
Furthermore, in the second, third, and fourth apparatuses for displaying fluorescence information in accordance with the present invention, the fluorescence information displaying means may employ one of various displaying techniques. For example, in cases where the light intensity of the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within a predetermined wavelength region containing 480 nm, and the light intensity of the fluorescence components of the fluorescence, which fluorescence components have wavelengths falling within the entire measurement wavelength region, are detected and the information in accordance with the ratio between the two detected light intensities are displayed, the fluorescence information displaying means may be constituted so as to display the ratio between the two detected light intensities on a monitor, with a printer, or the like. Alternatively, the fluorescence information displaying means may be constituted so as to alter the tint or the luminance of the displayed color in accordance with the ratio between the two detected light intensities.
The first method of displaying fluorescence information and the first apparatus for displaying fluorescence information in accordance with the present invention have the effects described below.
When the excitation light is irradiated to living body tissues, the living body tissues are excited by the excitation light and produce the fluorescence having a spectrum illustrated in FIG. 5. It is assumed that the thus produced fluorescence results from superposition of the fluorescence produced by various kinds of intrinsic dyes in the living body, such as FAD, collagen, fibronectin, and porphyrin. FIG. 5 shows typical fluorescence spectra of the fluorescence produced from normal tissues and the fluorescence produced from diseased tissues, which fluorescence spectra have been measured by the inventors.
As illustrated in FIG. 5, the level and the pattern of the spectrum of the fluorescence vary for the normal tissues and the diseased tissues. The level of the fluorescence produced from the normal tissues is high as a whole, and the level of the fluorescence produced from the diseased tissues is low as a whole. The fluorescence spectrum obtained from the normal tissues has a peak spectral intensity at a region in the vicinity of 480 nm, which region is a blue region. The fluorescence spectrum obtained from the diseased tissues has a peak spectral intensity at a region in the vicinity of 630 nm, which region is a red region, and a peak spectral intensity at a region in the vicinity of 700 nm.
FIG. 6 is a graph showing a distribution of ratios of spectral intensities at respective wavelengths of a fluorescence spectrum, which is obtained from normal tissues, to a spectral intensity of an entire measurement wavelength region width, which spectral intensity is taken as 1, and a distribution of ratios of spectral intensities at respective wavelengths of a fluorescence spectrum, which is obtained from diseased tissues, to a spectral intensity of the entire measurement wavelength region width, which spectral intensity is taken as 1. As illustrated in FIG. 6, the distributions of the spectral intensity ratios more clearly manifest the difference between the pattern of the fluorescence spectrum of the fluorescence produced from the normal tissues and the pattern of the fluorescence spectrum of the fluorescence produced from the diseased tissues.
In accordance with FIG. 5 and FIG. 6, the inventors studied about an appropriate combination of detection wavelengths, at which the difference between the pattern of the fluorescence spectrum obtained from the normal tissues and the pattern of the fluorescence spectrum obtained from the diseased tissues occurs markedly.
As a result, it has been found that, in cases where the light intensity at the wavelength region in the vicinity of 480 nm and the light intensity at the wavelength region in the vicinity of 630 nm or in the vicinity of 700 nm are detected, the ratio between the two detected light intensities markedly represents the difference between the pattern of the fluorescence spectrum obtained from the normal tissues and the pattern of the fluorescence spectrum obtained from the diseased tissues.
Specifically, the light intensity at the predetermined wavelength region containing 480 nm, at which a high light intensity is obtained characteristically from the normal tissues, and the light intensity at the predetermined wavelength region containing 630 nm or 700 nm, at which a high light intensity is obtained characteristically from the diseased tissues, are detected from the fluorescence having been detected from the measuring site, whose tissue state is unknown. Also, the information in accordance with the ratio between the two detected light intensities is displayed. In such cases, a person, who sees the displayed information, is capable of presuming whether the tissues at the measuring site are the normal tissues or the diseased tissues.
As described above, with the first method of displaying fluorescence information and the first apparatus for displaying fluorescence information in accordance with the present invention, the excitation light is irradiated to the measuring site in the living body, the excitation light causing the measuring site to produce the fluorescence. Also, the light intensity of the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the predetermined wavelength region containing 480 nm, is detected. Further, the light intensity of the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the predetermined wavelength region containing either one of 630 nm and 700 nm. Thereafter, the information in accordance with the ratio between the two detected light intensities is displayed. Therefore, with the first method of displaying fluorescence information and the first apparatus for displaying fluorescence information in accordance with the present invention, the information having enhanced reliability is capable of being displayed.
In the first apparatus for displaying fluorescence information in accordance with the present invention, the first fluorescence intensity detecting means may comprise the first wavelength selecting means for selecting the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the predetermined wavelength region containing 480 nm, and the first light intensity detecting means for detecting the light intensity of the fluorescence components having been selected by the first wavelength selecting means. Also, the second fluorescence intensity detecting means may comprise the second wavelength selecting means for selecting the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the predetermined wavelength region containing either one of 630 nm and 700 nm, and the second light intensity detecting means for detecting the light intensity of the fluorescence components having been selected by the second wavelength selecting means. With the thus modified first apparatus for displaying fluorescence information in accordance with the present invention, the light intensity at each of the predetermined wavelength regions is capable of being detected easily.
Also, from the results of analysis made on the fluorescence spectra illustrated in FIG. 5 and FIG. 6, it has been found that, if the width of the predetermined wavelength region containing 480 nm is broader than 480 nmxc2x170 nm, the ratio of the light intensity at the predetermined wavelength region detected from the diseased tissues to the light intensity at the predetermined wavelength region detected from the normal tissues will become high. Further, it has been found that, if the width of the predetermined wavelength region containing 630 nm is broader than 630 nm xc2x170 nm, or if the width of the predetermined wavelength region containing 700 nm is broader than 700 nmxc2x170 nm, the ratio of the light intensity at the predetermined wavelength region detected from the diseased tissues to the light intensity at the predetermined wavelength region detected from the normal tissues will become low. Therefore, with the first apparatus for displaying fluorescence information in accordance with the present invention, wherein the first wavelength selecting means selects the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the predetermined wavelength region of 480 nm xc2x1at most 70 nm, and the second wavelength selecting means selects the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the predetermined wavelength region of either one of 630 nmxc2x1at most 70 nm and 700 nmxc2x1at most 70 nm, the light intensity ratio having reliability enhanced even further is capable of being obtained.
Further, with the first apparatus for displaying fluorescence information in accordance with the present invention, wherein the excitation light has wavelengths falling within the range of 380 nm to 420 nm that is apart from the region in the vicinity of 480 nm, at which the light intensity of the fluorescence produced from the normal tissues becomes characteristically high, the fluorescence having the fluorescence spectrum of a desirable pattern is capable of being produced, and therefore the reliability of the displayed information is capable of being enhanced. Furthermore, with the first apparatus for displaying fluorescence information in accordance with the present invention, wherein the GaN type of semiconductor laser is employed as the excitation light irradiating means, the size of the apparatus is capable of being kept small, and the cost of the apparatus is capable of being kept low.
The second, third, and fourth methods of displaying fluorescence information and the second, third, and fourth apparatuses for displaying fluorescence information in accordance with the present invention have the effects described below.
As illustrated in FIG. 5, the level and the pattern of the spectrum of the fluorescence vary for the normal tissues and the diseased tissues. The level of the intrinsic fluorescence produced from the normal tissues is high as a whole, and the level of the intrinsic fluorescence produced from the diseased tissues is low as a whole. The fluorescence spectrum obtained from the normal tissues has a peak spectral intensity at a region in the vicinity of 480 nm, which region is the blue region. However, at the region in the vicinity of 480 nm, only slight fluorescence is produced from the diseased tissues. From FIG. 5, it can be found that the wavelengths, at which the difference between the spectral intensity of the fluorescence spectrum obtained from the normal tissues and the spectral intensity of the fluorescence spectrum obtained from the diseased tissues occurs markedly, are the wavelengths in the vicinity of 480 nm, and the wavelength of 480 nm is desirable as the center wavelength of the detection wavelengths.
Also, in experiments made by the inventors and with respect to a plurality of patients, fluorescence spectra of the fluorescence produced from diseased tissues and the fluorescence produced from normal tissues located in the vicinity of the diseased tissues were detected. Thereafter, from each of the fluorescence spectra, light intensities at various measurement wavelength regions having different widths and having their centers at 480 nm were calculated. With respect to each of the widths of the measurement wavelength regions, the ratio of the light intensity of the fluorescence produced from the diseased tissues to the light intensity of the fluorescence produced from the normal tissues was calculated. From the calculations, the results shown in FIG. 11 were obtained.
From the results shown in FIG. 11, it can be found that, in cases where the width of the measurement wavelength region is at most 100 nm, i.e. in cases where the measurement wavelength region is 480 nm at most 50 nm, little change occurs in the ratio of the light intensity of the fluorescence produced from the diseased tissues to the light intensity of the fluorescence produced from the normal tissues. Also, it can be found that, in cases where the width of the measurement wavelength region is 150 nm, the ratio of the light intensity of the fluorescence produced from the diseased tissues to the light intensity of the fluorescence produced from the normal tissues becomes high and close to 1, and the contrast between the fluorescence produced from the normal tissues and the fluorescence produced from the diseased tissues becomes low. Therefore, it can be found desirable to extract the fluorescence components having wavelengths falling within the wavelength region width of at most 140 nm around the wavelength of 480 nm, i.e. the wavelengths falling within the wavelength region of 480 nmxc2x1at most 70 nm, at which wavelength region little increase occurs with the ratio of the light intensity of the fluorescence produced from the diseased tissues to the light intensity of the fluorescence produced from the normal tissues.
Further, from the results of experiments, it has been found that the wavelength corresponding to the peak spectral intensity in the fluorescence spectrum often varies slightly for different persons and different measuring sites in a single person, and therefore the light intensity at the wavelength region, which at least contains 450 nm to 480 nm, should be detected.
FIG. 6 shows the distribution of ratios of spectral intensities at respective wavelengths of the fluorescence spectrum, which is obtained from the normal tissues, to the spectral intensity of the entire measurement wavelength region width, which spectral intensity is taken as 1, and the distribution of ratios of spectral intensities at respective wavelengths of the fluorescence spectrum, which is obtained from the diseased tissues, to the spectral intensity of the entire measurement wavelength region width, which spectral intensity is taken as 1. In cases where the ratios of the spectral intensities at respective wavelengths of the fluorescence spectrum to the spectral intensity of the entire measurement wavelength region width are calculated, adverse effects of a difference in measurement conditions, such as a measurement distance, can be eliminated. Therefore, the distributions of the spectral intensity ratios manifest the difference between the pattern of the fluorescence spectrum of the fluorescence produced from the normal tissues and the pattern of the fluorescence spectrum of the fluorescence produced from the diseased tissues. The fluorescence spectrum obtained from the normal tissues has the peak spectral intensity at the region in the vicinity of 480 nm. The fluorescence spectrum obtained from the diseased tissues has the peak spectral intensity at the region in the vicinity of 630 nm, and the peak spectral intensity at the region in the vicinity of 700 nm.
In accordance with FIG. 6, the inventors studied about measurement wavelengths and measurement wavelength region width, at which the difference between the pattern of the fluorescence spectrum obtained from the normal tissues and the pattern of the fluorescence spectrum obtained from the diseased tissues occurs markedly. The study was made in the same manner as that described above and by setting the center wavelengths at 480 nm, 630 nm, and 700 nm. FIG. 12 shows the results obtained from experiments, in which the center wavelength was set at 480 nm, the measurement wavelength region width was set at various different values, the ratio of the light intensity of each measurement wavelength region width to the light intensity of the entire measurement wavelength region width was calculated with respect to each of the fluorescence produced from the normal tissues and the fluorescence produced from the diseased tissues, and the ratio of the thus calculated light intensity ratio for the diseased tissues to the thus calculated light intensity ratio for the normal tissues was calculated.
As a result, from the study made with the spectral intensity ratio distribution, as in the study made with the spectral intensity distribution, in cases where the center wavelength is 480 nm, it has been found desirable to extract the fluorescence components having wavelengths falling within the wavelength region width of at most 140 nm around the wavelength of 480 nm, i.e. the wavelengths falling within the wavelength region of 480 nmxc2x1at most 70 nm and at least containing 450 nm to 480 nm, at which wavelength region little increase occurs with the ratio of the light intensity of the fluorescence produced from the diseased tissues to the light intensity of the fluorescence produced from the normal tissues and the contrast between the fluorescence produced from the normal tissues and the fluorescence produced from the diseased tissues does not become low.
Also, though not shown, in cases where the center wavelength is set at 630 nm, it has been found desirable to extract the fluorescence components having wavelengths falling within the wavelength region of 630 nmxc2x1at most 70 nm and at least containing 600 nm to 630 nm. Further, in cases where the center wavelength is set at 700 nm, it has been found desirable to extract the fluorescence components having wavelengths falling within the wavelength region of 700 nmxc2x1at most 70 nm and at least containing 700 nm to 710 nm.
Specifically, the fluorescence components having the wavelengths falling within the wavelength region described above are extracted from the fluorescence having been detected from the measuring site, whose tissue state is unknown, and the light intensity of the extracted fluorescence components is detected. Also, the information in accordance with the detected light intensity is displayed. In such cases, a person, who sees the displayed information, is capable of accurately presuming whether the tissues at the measuring site are the normal tissues or the diseased tissues.
As described above, with the second method of displaying fluorescence information and the second apparatus for displaying fluorescence information in accordance with the present invention, the excitation light is irradiated to the measuring site in the living body, the excitation light causing the measuring site to produce the fluorescence. Also, the light intensity B of the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the wavelength region of 480 nm xc2x1at most 70 nm and at least containing 450 nm to 480 nm, is detected. Further, the information in accordance with the light intensity B is displayed. Therefore, with the second method of displaying fluorescence information and the second apparatus for displaying fluorescence information in accordance with the present invention, the information having enhanced reliability is capable of being displayed.
With the third method of displaying fluorescence information and the third apparatus for displaying fluorescence information in accordance with the present invention, the excitation light is irradiated to the measuring site in the living body, the excitation light causing the measuring site to produce the fluorescence. Also, the light intensity W of the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the entire measurement wavelength region, is detected. Further, at least one light intensity is detected, the at least one light intensity being selected from among the light intensity Bxe2x80x2 of the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the wavelength region of 480 nmxc2x1at most 70 nm and at least containing 450 nm to 480 nm, the light intensity R1 of the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the wavelength region of 630 nm xc2x1at most 70 nm and at least containing 600 nm to 630 nm, and the light intensity R2 of the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the wavelength region of 700 nmxc2x1at most 70 nm and at least containing 700 nm to 710 nm. Furthermore, the information in accordance with the ratio between the at least one selected light intensity and the light intensity W is displayed. Therefore, with the third method of displaying fluorescence information and the third apparatus for displaying fluorescence information in accordance with the present invention, adverse effects of fluctuations in spectral intensity due to fluctuations in measurement conditions, such as the measurement distance and the measurement angle, are capable of being reduced, and the information having enhanced reliability, which represents the feature of the spectrum pattern, is capable of being displayed.
With the fourth method of displaying fluorescence information and the fourth apparatus for displaying fluorescence information in accordance with the present invention, the excitation light is irradiated to the measuring site in the living body, the excitation light causing the measuring site to produce the fluorescence. Also, the light intensity B of the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the wavelength region of 480 nmxc2x1at most 70 nm and at least containing 450 nm to 480 nm, is detected. Further, the light intensity W of the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the entire measurement wavelength region, is detected. Furthermore, at least one light intensity is detected, the at least one light intensity being selected from among the light intensity Bxe2x80x2 of the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the wavelength region of 480 nmxc2x1at most 70 nm and at least containing 450 nm to 480 nm, the light intensity R1 of the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the wavelength region of 630 nm xc2x1at most 70 nm and at least containing 600 nm to 630 nm, and the light intensity R2 of the fluorescence components of the fluorescence produced by the measuring site, which fluorescence components have wavelengths falling within the wavelength region of 700 nmxc2x1at most 70 nm and at least containing 700 nm to 710 nm. Also, the information in accordance with the light intensity B and the ratio between the at least one light intensity, which is selected from among the light intensities Bxe2x80x2, R1, and R2, and the light intensity W is displayed. Therefore, with the fourth method of displaying fluorescence information and the fourth apparatus for displaying fluorescence information in accordance with the present invention, the information having enhanced reliability, which represents the characteristics of the spectral intensity and the spectrum pattern, is capable of being displayed.
With the second, third, and fourth apparatuses for displaying fluorescence information in accordance with the present invention, wherein each of the light intensity detecting means is provided with the image sensor for two-dimensionally detecting the fluorescence produced by the measuring site and forming a fluorescence image, the information concerning the fluorescence over a wide range is capable of being displayed quickly.
With the second, third, and fourth apparatuses for displaying fluorescence information in accordance with the present invention, wherein each of the light intensity detecting means is provided with the fluorescence acquiring means for acquiring the fluorescence, which is produced by a single point at a site in the living body, the information concerning the fluorescence produced from a desired point at the site is capable of being displayed.
With the second, third, and fourth apparatuses for displaying fluorescence information in accordance with the present invention, wherein the excitation light has the wavelengths falling within the range of 380 nm to 420 nm that is apart from the region in the vicinity of 480 nm, at which region the light intensity of the fluorescence produced from normal tissues takes the characteristically large value, the fluorescence with the fluorescence spectrum in a desirable pattern is capable of being produced, and the reliability of the displayed information is capable of being enhanced. Furthermore, with the second, third, and fourth apparatuses for displaying fluorescence information in accordance with the present invention, wherein the GaN type of semiconductor laser is employed as the excitation light irradiating means, the size of the apparatus is capable of being kept small, and the cost of the apparatus is capable of being kept low.