JP6391955B2 - Inspection device using laparoscope - Google Patents

Description

  The present invention relates to an inspection method and an inspection apparatus using a laparoscope, and more particularly to an inspection method and an inspection apparatus that provide information for determining cancer cell / cancer tissue metastasis to a sentinel lymph node.

  In general, in solid cancer surgery, a lesion is removed and a plurality of lymph nodes that are suspected of metastasis around the lesion are often removed (referred to as “lymph node cleansing”). Lymph node dissection is effective for the cure of cancer. However, for example, in the case of limited to early gastric cancer, the ratio of metastasis to lymph nodes is about 3% to 10%, and unnecessary lymph node cleansing has been performed for 90% or more patients who have not metastasized. There is a drawback that the burden on the patient is large.

  The lymph node to which the cancer cells that have entered the lymphatic vessels from the primary lesion of the cancer first arrive is called a sentinel-lymph-node, and whenever the cancer has spread to the lymph node, it is always sentinel lymph node. Is considered to have metastasis (this is called sentinel lymph node theory). According to the sentinel lymph node theory, in early cancer surgery, a sentinel lymph node is found, a biopsy (inspected by examining a part of the affected area with a microscope, etc.), and a rapid pathological examination is performed. The presence or absence of cancer metastasis to can be determined. When the cancer has not spread to the sentinel lymph node, only the lesioned part can be removed by laparoscopic surgery, or lymph node cleansing itself becomes unnecessary. On the other hand, when cancer has metastasized to the sentinel lymph node, lymph node disinfection according to the metastatic state is required. For example, in the case of gastric cancer that has metastasized to lymph nodes, excision of at least 1/2 of the stomach with lymph node dissection is required.

  These lymph nodes are outside the organ. Therefore, it cannot be detected with an endoscope whether there is cancer metastasis, and must be observed from outside the organ.

  In recent years, a fluorescent dye method for detecting a diseased tissue using a fluorescent dye has been proposed. For example, Patent Document 1 discloses that a photosensitive substance that emits fluorescence by excitation light (for example, a cyanine dye) is preliminarily administered to a living body as a fluorescent diagnostic agent, and is irradiated with excitation light in the excitation wavelength band of the photosensitive substance. A method has been proposed in which fluorescence is generated from a photosensitive substance accumulated in a region, the generated fluorescence is received, and a localized range and an infiltration range of a lesion are detected. This method has also been proposed to be applicable to sentinel lymph nodes.

  Patent Document 2 proposes a detection system for easily and accurately detecting such sentinel lymph nodes from the surface of a living tissue. This detection system is a system that injects indocyanine green, which is a near-infrared fluorescent dye, locally around the tumor in advance, performs laparotomy after a predetermined time, and emits indocyanine green by irradiating the observation part with excitation light It is. Specifically, as shown in FIG. 2 of the same document, the observation unit is irradiated with near-infrared excitation light from the excitation light irradiation unit. Since indocyanine green is accumulated in the sentinel lymph node, the indocyanine green emits near-infrared fluorescence, and the near-infrared fluorescence is amplified by an image intensifier and converted into a visualized image by a fluorescent screen. The An observer observes simultaneously the normal image which permeate | transmitted the half mirror, and the visualization image which reflected the mirror and the half mirror. Since the excitation light and fluorescence are light of near infrared wavelength that is difficult to be absorbed by living tissue such as fat covering the sentinel lymph node, the sentinel lymph node can be detected from the surface of the living tissue.

  Since laparotomy is a heavy burden on the patient, recently, for example, a non-laparotomy operation using a laparoscope as shown in Patent Document 3 has been performed. The laparoscope described in Patent Document 3 is used for diagnosis by inserting a laparoscope from a small hole opened in a patient and acquiring an image of the affected area. The laparoscope proposed in the same document has a distal end portion of a predetermined length to be inserted, and a mechanism for acquiring an image of the affected area and transmitting the acquired image of the affected area is provided at the distal end portion. . The image transmission mechanism is a long sheath tube formed of a rigid member, and is placed within the sheath tube to flow fluid across the outer surface of the image transmission means, from which it interferes with the image Means for removing objects.

  Patent Document 4 proposes a laparoscopic diagnostic apparatus and a sentinel lymph node inspection method that can easily and quickly specify the position of the sentinel lymph node. According to this inspection method, the irradiation position and irradiation range of the white illumination light irradiated from the imaging laparoscope and the irradiation position and irradiation range of the excitation light irradiated from the excitation laparoscope can be changed. The search range of lymph nodes can be changed arbitrarily. Since the search by the laparoscope for excitation can be performed in a wider range than the observation range of the imaging laparoscope, the position search of the sentinel lymph node can be quickly performed. In addition, since the excitation light is emitted from the excitation laparoscope toward the observation target of the white illumination light irradiated by the imaging laparoscope, it is obtained from the color image obtained from the reflected light of the white illumination light and the fluorescence emitted from the fluorescent material. The obtained fluorescence image can be obtained in a superimposed manner by the same imaging laparoscope and displayed on the monitor. Further, the image acquisition and the fluorescence spectrum acquired by the fluorescence spectroscopic measurement unit can be acquired simultaneously and displayed on the monitor.

International Publication WO 98/48845 JP 2001-299676 A JP-A-6-22902 JP 2013-153951 A

  In the current operation, cancer metastasis to the sentinel lymph node cannot be determined immediately because it is determined by biopsy (pathological examination) of the sentinel lymph node obtained by incision. Therefore, in visceral surgery, the same operation as in the case of metastasis is currently performed before confirming the biopsy result. For example, in the case of gastric cancer, about 60% is early cancer and may not have metastasized to the sentinel lymph node, and surgery is also performed on such patients, which places a heavy burden on the patients. become.

  The technique proposed in Patent Document 2 is a laparoscope in which a laparoscope that emits excitation light and a laparoscope that emits white illumination light are the same. Therefore, since the excitation light to be irradiated is irradiated over a wide range of the observation part, when the fluorescent substance bound to the cancer cell is a very small amount, the fluorescent substance emits only weak fluorescence, and the cancer is Identifying metastatic sentinel lymph nodes is extremely difficult. In addition, conventionally, a device that switches between excitation light and white illumination light is used to alternately irradiate and is not affected by white illumination light at the time of fluorescence measurement. When the mirror is used, there is an advantage that the irradiation position of the excitation light and the irradiation position of the white illumination light coincide with each other. However, since the irradiation position and irradiation range cannot be changed by the excitation light and the white illumination light, when searching for the sentinel lymph node, the search range is limited to the irradiation range of the laparoscope, and the position of the sentinel lymph node is changed. There was a limit to searching accurately and quickly. For this reason, searching for sentinel lymph nodes to examine cancer metastasis has been limited.

  Further, in the technique proposed in Patent Document 2, the visible light image and the fluorescent image are located at exactly the same position due to causes such as the inability to continuously measure the fluorescent image, the movement of the organ, or the laparoscopic camera shake. There is a problem that it cannot be observed and the detection accuracy of the sentinel lymph node is lowered. For this reason, there is a demand for simultaneous measurement of a visible light image and a fluorescent image. Furthermore, the technique proposed in Patent Document 2 cannot measure in detail the temporal change in fluorescence intensity since the injection of the fluorescent substance (test reagent), and it is difficult to grasp the optimal detection time of the sentinel lymph node. The detection efficiency and detection accuracy of lymph nodes have not been optimized, and both need to be improved. Further, since the excitation light and the white illumination light are simultaneously irradiated, there is a problem that noise in the fluorescence wavelength band due to the white illumination light is generated and the fluorescence sensitivity is deteriorated. In addition, the detection of sentinel lymph nodes was determined from the shape of the lymph and the relative luminance on the monitor, but the relative luminance depends on the time since administration of the fluorescent substance (test reagent) or injection, so it is appropriate. It is necessary to select and judge an image of a long time, and there is a concern that a measurement error increases depending on the position of the sentinel lymph node.

  In addition, even if the position of the sentinel lymph node is known, it is necessary to remove the sentinel lymph node and perform a pathological examination to determine whether cancer has metastasized to the sentinel lymph node. Therefore, it took time to wait for the result of the pathological examination, and the burden on the patient was great. If rapid pathological examination cannot be performed, conventional major lymph node dissection has been performed. For these reasons, examination of metastasis to sentinel lymph nodes in situ with a laparoscope is desired.

  In addition, the technique proposed in Patent Document 3 can wash the laparoscope in order to prevent the laparoscope from being soiled and unable to pick up an image when taking the image with the laparoscope. Therefore, no technique has been proposed for identifying lesions caused by cancer and examining cancer metastasis.

  The technique proposed in Patent Document 4 relates to a diagnostic apparatus and an inspection method that can easily and quickly identify the position of the sentinel lymph node using a laparoscope, but about a technique for examining cancer metastasis. Not proposed.

  The present invention has been made to solve the above-mentioned problems, and its purpose is to specify the exact position of the sentinel lymph node, to examine the sentinel lymph node with high sensitivity and high resolution, and to detect cancer cells. The object is to provide an inspection method and an inspection apparatus capable of providing information for determining whether or not cancer tissue has metastasized.

(1) An inspection method according to the present invention for solving the above-described problem uses at least two laparoscopes, and provides information for determining the metastasis of cancer cells / cancer tissues to sentinel lymph nodes within the observation range. An inspection method to be provided,
The visible light image obtained by irradiating the observation range with illumination light and the first fluorescence image obtained by irradiating the observation range with the first excitation light are superimposed and displayed, and the position of the sentinel lymph node A position confirmation step to confirm,
A second excitation light irradiation step of irradiating a second excitation light in accordance with the size of the sentinel lymph node to the sentinel lymph node selected from the sentinel lymph nodes whose positions have been confirmed;
A second fluorescence image displaying step of receiving a second fluorescence obtained by irradiating the second excitation light and displaying a second fluorescence image; and a second fluorescence image displaying step obtained by irradiating the second excitation light. One or both of the fluorescence spectrum display steps for measuring and displaying the fluorescence spectrum from the two fluorescences.

  In the inspection method according to the present invention, the second fluorescent image and the first fluorescent image are displayed in a superimposed manner, or the second fluorescent image and the visible light image are displayed in a superimposed manner. be able to.

  (2) An inspection apparatus according to the present invention for solving the above-described problems uses at least two laparoscopes and provides information for determining whether cancer cells / cancerous tissues have metastasized to sentinel lymph nodes within the observation range. An inspection apparatus to be provided, wherein any one of the laparoscopes includes the following (A) to (E).

(A) Illumination light irradiation means for irradiating the observation range with illumination light;
(B) a first excitation light irradiation means for irradiating the observation range with the first excitation light;
(C) Second excitation light irradiation means for irradiating the sentinel lymph node with second excitation light,
(D) Visible light obtained by irradiating the illumination light, first fluorescence emitted from the sentinel lymph node detecting fluorescent material obtained by irradiating the first excitation light, and the second excitation. Image capturing means for receiving and imaging the second fluorescence emitted from the fluorescent substance for cancer cell / cancer tissue detection obtained by irradiating with light;
(E) The first fluorescence emitted from the observation range obtained by irradiating the first excitation light and the cancer cell / cancer tissue detection fluorescent substance obtained by irradiating the second excitation light. Fluorescence measuring means for receiving the second fluorescence and measuring the fluorescence.

  In the inspection apparatus according to the present invention, a first laparoscope of the laparoscopes includes the image capturing means, and a second laparoscope of the laparoscopes includes the illumination light irradiation means and the first One excitation light irradiation means, the second excitation light irradiation means, and the first and second fluorescence measurement means can be provided.

  In the inspection apparatus according to the present invention, the first laparoscope of the laparoscopes includes the illumination light irradiation means and the image capturing means, and the second laparoscope of the laparoscopes includes the The first excitation light irradiation means, the second excitation light irradiation means, and the first and second fluorescence measurement means can be provided.

In the inspection apparatus according to the present invention,
An illumination light source for irradiating the illumination light;
A first excitation light source for irradiating the first excitation light;
A second excitation light source for irradiating the second excitation light;
A visible light imaging device for imaging the visible light;
A fluorescence imaging device for imaging the first fluorescence or the second fluorescence;
An image processing device for processing image information obtained by the visible light imaging device and the fluorescence imaging device;
A fluorescence spectrum measuring device for measuring a fluorescence spectrum from the first and second fluorescence;
A control device for controlling each light source and device;
A display device for displaying an output result from the device;
Can be configured to include at least.

  According to the inspection method and the inspection apparatus according to the present invention, whether or not there is metastasis of cancer cells / cancer tissues by identifying the exact position of the sentinel lymph node, inspecting the sentinel lymph node with high sensitivity and high resolution, and It is possible to provide information for judging.

  Specifically, according to this inspection method and inspection apparatus, the position is captured by fluorescent images generated from lymph vessels / lymph nodes, cancer cells / cancerous tissues, and fluorescence generated by excitation light irradiation is received from the spectrum information. Since it is possible to confirm whether the position information is correct, information on the presence or absence of cancer metastasis can be obtained on the spot. Based on the obtained test results, other test results, and diagnosis by a doctor, it is possible to make a judgment on cancer metastasis in a short time, which can help to determine an appropriate treatment policy. When surgery is required, the operation time can be shortened, and unnecessary lymph node cleansing can be eliminated, thereby reducing the burden on the patient.

It is the block diagram which shows an example (case 1) of the inspection apparatus which concerns on this invention, and explanatory drawing which shows a position observation step. It is explanatory drawing which shows a 2nd excitation light irradiation step using the test | inspection apparatus of FIG. It is the block diagram which shows other examples (case 2) of the inspection apparatus which concerns on this invention, and explanatory drawing which shows a position observation step. It is explanatory drawing which shows a 2nd excitation light irradiation step using the test | inspection apparatus of FIG. It is a block diagram which shows another example (three laparoscopes) of the test | inspection apparatus which concerns on this invention. 4 is a cross-sectional view showing an example of a laparoscope for exciting light irradiation used in the inspection apparatus of case 1. FIG. 6 is a cross-sectional view showing an example of an imaging laparoscope used in the inspection apparatus of case 1. FIG. 6 is a cross-sectional view showing another example of a laparoscope for exciting light irradiation used in the inspection apparatus of case 1. FIG. 7 is a cross-sectional view showing an example of a laparoscope for exciting light irradiation used in the inspection apparatus of case 2. FIG. 6 is a cross-sectional view showing an example of an imaging laparoscope used in the inspection apparatus of case 2. FIG. It is a block diagram which shows an example of the laparoscope for imaging using a relay lens system, an imaging device, and an image process part. It is a block diagram which shows an example of the imaging device and image processing part which are connected to the laparoscope for imaging. It is explanatory drawing which shows an example of the display image of a monitor. It is a structural example of an imaging device. It is explanatory drawing which shows an example of a fluorescence measurement part. It is explanatory drawing which shows another example of a fluorescence measurement part.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings. The technical scope of the present invention is not limited only to the following description and drawings.

[Inspection method]
As shown in FIGS. 1 to 4, the examination method according to the present invention uses at least two laparoscopes 10 and 20 to determine whether cancer cells / cancer tissues have metastasized to the sentinel lymph node S within the observation range P. It is an inspection method that provides information for. And the main structure is the step which confirms the position of the sentinel lymph node S, the step which irradiates the 2nd excitation light C, the step which displays a 2nd fluorescence image, and / or the display step which displays a fluorescence spectrum And having.

  Specifically, as shown in FIGS. 1 and 3, the position confirmation step irradiates the observation range P with the visible light image obtained by irradiating the illumination light A and the observation range P with the first excitation light B. In this step, the obtained first fluorescent image is superimposed and displayed to confirm the position of the sentinel lymph node. As shown in FIG. 2 and FIG. 4, the second excitation light irradiation step is a second step in which the sentinel lymph node S selected from the sentinel lymph nodes whose positions have been confirmed is adjusted to the size of the sentinel lymph node S. This is a step of irradiating the excitation light C. As shown in FIGS. 2 and 4, the display step receives the second fluorescence c obtained by irradiating the second excitation light C and displays a second fluorescence image (second fluorescence image). One or both of a display step and a step of measuring and displaying a fluorescence spectrum from the second fluorescence c obtained by irradiating the second excitation light C (referred to as a fluorescence spectrum display step). It is a step.

  Whether or not there is metastasis of cancer cells / tissues by identifying the exact position of the sentinel lymph node S and examining the sentinel lymph node S with high sensitivity and high resolution by configuring the inspection method in the above steps. Information for determining whether or not can be provided. More specifically, the position of the first excitation light A can be captured by a fluorescence image obtained by imaging the first fluorescence generated from the lymph vessels and lymph nodes by the irradiation of the first excitation light A. Information on the presence or absence of cancer cell / cancer tissue metastasis can be obtained on the spot from the spectrum information obtained by measuring the second fluorescence c generated from the sentinel lymph node S by irradiation. Based on the obtained test results, other test results, and diagnosis by a doctor, it is possible to make a determination of metastasis of cancer cells / cancer tissues in a short time, which can be useful for determining an appropriate treatment policy. When surgery is required, the operation time can be shortened, and unnecessary lymph node cleansing can be eliminated, thereby reducing the burden on the patient.

  The inspection method according to the present invention is extremely effective in dealing with early cancer. For example, when the cancer is visible from outside the stomach by a laparoscope, it is no longer an early cancer, and a surgery to largely remove the stomach is generally performed. In the present invention, as shown in FIG. 13 (A), when the presence and approximate position of a cancerous lesion C ′ are known in advance by other general examination means, the cancer of the lesioned C ′ is near. It is an inspection method in which the sentinel lymph node S near the lesioned part C ′ is inspected to determine whether or not it has metastasized to provide judgment information.

[Inspection equipment]
As shown in FIGS. 1 to 4, the inspection apparatus 1 according to the present invention uses at least two laparoscopes 10 and 20 to detect cancer cell / cancer tissue metastasis to the sentinel lymph node S within the observation range P. This is an inspection device that provides information for judgment. And any one of the laparoscopes 10 and 20 is characterized by including the following means (A) to (E).

(A) Illumination light irradiation means for irradiating the observation range P with the illumination light A,
(B) First excitation light irradiation means for irradiating the observation range P with the first excitation light B,
(C) Second excitation light irradiation means for irradiating the sentinel lymph node S with the second excitation light C,
(D) Visible light a obtained by irradiating illumination light A, first fluorescence b emitted from a fluorescent material for sentinel lymph node detection obtained by irradiating first excitation light B, and second excitation Image capturing means for receiving and imaging the second fluorescence c emitted from the fluorescent substance for cancer cell / cancer tissue detection obtained by irradiating the light C;
(E) Fluorescence for cancer cell / cancer tissue detection obtained by irradiating the first excitation light B and the first fluorescence b emitted from the observation range P and the second excitation light C obtained by irradiating the first excitation light B Fluorescence measuring means for receiving the second fluorescence c emitted from the substance and measuring the fluorescence.

  This inspection method mainly uses an inspection apparatus 1 (1A, 1B) composed of two laparoscopes 10 and 20 as shown in FIGS. 1 to 4, but as shown in FIG. You may use the test | inspection apparatus (1C) comprised by the three laparoscopes 10, 20, and 30. FIG.

  Below, the inspection apparatus 1 using the two laparoscopes 10 and 20 is demonstrated.

  1A and 2B, the laparoscope 10 includes an illumination light irradiation function, a first excitation light irradiation function, a first fluorescence light receiving function, a second excitation light irradiation function, The laparoscope 20 is responsible for the imaging function. On the other hand, in the inspection apparatus 1B of Case 2 shown in FIGS. 3 and 4, the laparoscope 10 has a first excitation light irradiation function, a first fluorescence light reception function, a second excitation light irradiation function, and a second fluorescence light reception function. The laparoscope 20 has an illumination light irradiation function and an imaging function. In the inspection apparatus 1C shown in FIG. 5, the laparoscope 10 is responsible for the illumination light irradiation function and the first excitation light irradiation function, and the laparoscope 20 is the first fluorescence light reception function and the second excitation light irradiation function. And the second fluorescent light receiving function, and the laparoscope 30 has the imaging function.

[Inspection method / Case 1]
First, an inspection method when the case 1 inspection apparatus 1A is used will be described. As described above, the inspection method includes the step of confirming the position of the sentinel lymph node S, the step of irradiating the second excitation light C, the display step of displaying the second fluorescence image, and / or the display step of displaying the fluorescence spectrum. And have. In the inspection apparatus 1A of Case 1 used here, the laparoscope 10 has an illumination light irradiation function, a first excitation light irradiation function, a first fluorescence light reception function, a second excitation light irradiation function, and a second fluorescence light reception function. The laparoscope 20 is responsible for the imaging function. The laparoscope 20 having the imaging function is also referred to as “imaging laparoscope 20”.

(Position observation step)
In the position confirmation step, as shown in FIG. 1, the visible light image obtained by irradiating the observation range P from the laparoscope 10 with the illumination light A and receiving the visible light a by the laparoscope 20 and the observation from the laparoscope 10 The position of the sentinel lymph node is confirmed by superimposing the first fluorescence image obtained by irradiating the range P with the first excitation light B and receiving the first fluorescence b with the laparoscope 20.

  First, before the examination, the patient is preliminarily administered with a first fluorescent substance that enters the lymph node and emits light by irradiation with the first excitation light B that is near infrared, or the first Fluorescent material is injected directly before testing. An example of the first fluorescent substance is indocyanine green. Furthermore, the patient is preliminarily administered with a second fluorescent substance that specifically binds to cancer cells / cancer tissues and emits light when irradiated with the second excitation light C. Examples of the second fluorescent substance include talaporphyrin, resaphyrin, hematoporphyrin, 5-aminolevulinic acid and the like.

  Then, two small insertion ports H are formed in the patient, carbon dioxide gas is injected into the abdomen and inflated, and the laparoscopes 10 and 20 are inserted into the two insertion ports H, respectively. After such preparation is completed, the illumination light A is irradiated from the laparoscope 10 to the observation range P of the imaging laparoscope 20. As the illumination light A, white light in the visible light region or the like is used. The visible light a reflected from the observation range P by the imaging laparoscope 20 is received, and the visible light a is guided to the imaging device 90. As shown in FIG. 12, the visible light a guided to the imaging device 90 passes through a dichroic mirror 92 provided in the imaging device 90 and is imaged by the CCD camera 93. The visible light image captured by the CCD camera 93 is supplied to the visible light image processing unit 120, subjected to visible light image processing, and stored in a recording device (not shown). As shown in FIG. 13A, the processed image is displayed on the monitor 200 as a visible light image in the observation range P in accordance with a display instruction. From the visible light image displayed on the monitor 200, the outside of the organ with the lesion C 'can be confirmed.

  As an illumination light irradiation light source for irradiating the illumination light A, a lamp such as a halogen lamp or a white LED light source can be used. As the first excitation light source for irradiating the first excitation light B, a near infrared light source such as a halogen lamp or an infrared laser light source can be used. Among these, when using a halogen lamp that emits light of a wide wavelength, it is preferable to cut the wavelength other than the wavelength band used for the visible light image to be viewed using an optical filter. For example, when a visible light image is captured, it is emitted from the near infrared ray irradiated from the first excitation light B that excites the first fluorescent substance or from the second excitation light C that excites the second fluorescent substance. It is preferable to use light having a wavelength necessary for forming a visible light image by cutting the wavelength to be cut by an optical filter. The same applies to the case of irradiating near infrared rays, and it is preferable to use light having a wavelength necessary for forming a visible light image by cutting unnecessary light with an optical filter. Selection of the wavelength is easy when a laser light source or an LED light source is used, and since there are few unnecessary wavelengths, the heat generation of the irradiation section can also be reduced.

  Next, as shown in FIG. 13B, the sentinel lymph node S existing in the peripheral portion of the lesion C ′ is specified. To identify the sentinel lymph node S, as shown in FIG. 1, the first excitation light source 60 is turned on, and the first excitation light B (near infrared) having a wavelength of 700 nm to 830 nm (as an example, 780 nm) is emitted from the laparoscope 10. Irradiated to the observation range P. When, for example, indocyanine green is administered to a patient as the first fluorescent substance, when indocyanine green is irradiated with near infrared light having a wavelength of 700 nm to 830 nm, the indocyanine green is fluorescent (wavelength of 830 nm to 850 nm). Emits fluorescence b).

  The first fluorescent light b thus emitted is received by the laparoscope 20 and guided to the imaging device 90. As shown in FIG. 12, the first fluorescence b guided to the imaging device 90 is guided to the near-infrared CCD camera 94 by the dichroic mirror 92, and the near-infrared CCD camera 94 images the first fluorescence b. To capture images. At this time, a second filter 96 is attached in front of the lens of the near-infrared CCD camera 94, and the first fluorescence b or the wavelength emitted by irradiation with the first excitation light B is 830 nm or more (for example, 850 nm) or Only the first fluorescent light b of 830 to 850 nm (850 nm as an example) is guided to the near infrared CCD camera 94 and imaged. The captured first fluorescence b is supplied to the fluorescence image processing unit 130, and the first fluorescence image processed by the fluorescence image processing unit 130 is displayed on the monitor 200 as shown in FIG. . Note that FIG. 13C shows a visible light image and a first fluorescent image superimposed on each other. Based on the display on the monitor 200, the sentinel lymph node S is specified by a doctor.

  It is important for the diagnosis based on the obtained result that the visible light image and the first fluorescent image are taken at the same position. For this purpose, it is convenient that both images can be taken with the laparoscope 20. It is also convenient that both the irradiation of the illumination light A and the irradiation of the first excitation light B can be performed with the laparoscope 10.

(Second excitation light irradiation step)
In the second excitation light irradiation step, as shown in FIG. 2, the sentinel lymph node S selected from among the sentinel lymph nodes S1, S2, S3, etc. whose position has been confirmed is adjusted to the size of the sentinel lymph node S. The second excitation light C is irradiated from the laparoscope 20.

  First, the second excitation light C is irradiated from the laparoscope 10 to the identified sentinel lymph node S. Since the patient is pre-administered with a second fluorescent substance that specifically binds to cancer cells / tissues, the second fluorescent substance is excited by irradiating the sentinel lymph node S with the second excitation light C. When the second fluorescence c peculiar to the second fluorescent substance is detected, the presence of cancer cells / cancerous tissues can be confirmed in the sentinel lymph node S. By these steps, it is possible to examine whether or not cancer cells / cancer tissues have metastasized to the sentinel lymph node S.

  The second excitation light C is light in the visible light region, and the second fluorescence c generated by the irradiation of the second excitation light C is also fluorescence in the visible light region. Since these wavelengths are determined by the type of the second fluorescent material, the second excitation light C having a wavelength corresponding to the type is irradiated. Examples of the second fluorescent substance include talaporphyrin, resaphyrin, hematoporphyrin, 5-aminolevulinic acid, and the like. Examples of the second excitation light C that generates the second fluorescence c from the second fluorescent material include light having a peak wavelength of 664 nm, and the resulting second fluorescence is 672 nm. Light having a peak wavelength of Further, as the second excitation light C, for example, light having a peak wavelength of 405 nm can be exemplified, and as the resulting second fluorescence c, light having a peak wavelength of 633 nm can be exemplified.

  The size to which the second excitation light C is applied is preferably the same size as the sentinel lymph node S to be irradiated. Therefore, the laparoscope 10 that irradiates the second excitation light B is provided with excitation light aperture means for irradiating the second excitation light C with the same size as the sentinel lymph node S. Yes. Since the sentinel lymph node S has an outer diameter of about 1 mm to 2 mm, the size of the second excitation light C in the laparoscope 10 is in the range of about 0.05 mm to 2.5 mm, which is the same as that of the sentinel lymph node S. Irradiate with the aperture narrowed. Preferably it is the range of 0.1 mm-1 mm. When the excitation light is reduced, the intensity of the excitation light is increased, so that the specified sentinel lymph node S can be irradiated with high intensity excitation light. By irradiating the second excitation light C with increased intensity, even if the second fluorescent substance contained in the sentinel lymph node S is in a trace amount, the second fluorescence intensity proportional to the intensity of the excitation light can be obtained. A relatively high fluorescence intensity can be obtained. In addition, if the focal position of the second excitation light C irradiated with the same size as the sentinel lymph node S is moved, the position of the cancer can be specified, and observation with high sensitivity and high resolution is also possible. become.

  Thus, the effect of applying the second excitation light C with the same size as that of the sentinel lymph node S is that fluorescence that becomes noise from cancer cells / cancer tissues existing around the sentinel lymph node to be examined is obtained. This can be reduced, leading to an increase in inspection accuracy.

(Display step)
In the display step, the second excitation light C is irradiated in the second excitation light irradiation step described above, and the obtained second fluorescence c is processed and displayed. In this display step, it is possible to arbitrarily select whether the display method is to display only the second fluorescence image, only the fluorescence spectrum, or both. That is, in this display step, the second fluorescence c generated by irradiating the second excitation light C is received by the laparoscope 20, and the received second fluorescence c is imaged to display a second fluorescence image. To do. In the fluorescence spectrum display step, the second fluorescence c generated by irradiating the second excitation light C is received by the laparoscope 20, and the fluorescence spectrum is measured and displayed from the received second fluorescence c. In this display step, the display of the second fluorescence image and the display of the fluorescence spectrum measurement result may be performed together, or only the second fluorescence image may be displayed, or only the display of the fluorescence spectrum measurement result may be performed. May be performed. When the display of the second fluorescence image and the display of the fluorescence spectrum measurement result are performed together, they may be displayed separately or displayed side by side.

  As shown in FIG. 2, the second fluorescence c generated by irradiating the second excitation light C is received by the laparoscope 10 and guided to the fluorescence measuring unit 80 by the fluorescence receiving optical fiber cable 27. . Note that the laparoscope 10 may be provided with a mark function such as a laser pointer for displaying the irradiation position of the second excitation light C so that the second excitation light C can be correctly irradiated to the specified sentinel lymph node S. Good. Various types of laser pointers can be used. For example, a green laser pointer can be used.

  When the fluorescence measuring unit 80 is a “fluorescence detector”, the fluorescence detector is set by selecting and providing an optical filter so as to detect only the wavelength of the second fluorescence c emitted from the second fluorescent material. Keep it. If this fluorescence detector detects the second fluorescence c emitted from the second fluorescence substance, the measurement result display control unit 160 displays on the monitor 200 that the fluorescence detector has detected the second fluorescence c. . Therefore, the doctor can determine whether or not the wavelength of the second fluorescence c emitted from the second fluorescent material has been detected based on the display on the monitor 200. If the fluorescence detector detects the second fluorescence c emitted by the second fluorescent substance and the result is displayed on the monitor 200, the sentinel lymph node S has the second fluorescence combined with cancer cells / cancer tissues. The substance will be present. In that case, it is found that cancer cells and cancer tissues have metastasized to the sentinel lymph node S.

  For example, as shown in FIG. 13C, when a first fluorescent image image-processed based on the first fluorescence a imaged by the near-infrared CCD camera 94 is displayed on the monitor 200, the position of the sentinel lymph node S is displayed. Can be identified visually. In this case, the superimposed image processing unit 140 can display the visible light image and the first fluorescent image on the monitor 200 in a superimposed manner so that the position can be visually grasped accurately. The superimposed image of the visible light image and the first fluorescent image is preferably a process of superimposing in real time.

  In addition, as shown in FIG. 13E, the sentinel lymph node can be easily inspected by adjusting the laparoscope 20 and the laparoscope 10 so that the sentinel lymph node to be inspected is at the center of the monitor. Specifically, a superimposed image is created at a position where the sentinel lymph node to be examined comes to the center of the monitor. The second fluorescence intensity obtained by irradiating the sentinel lymph node S with the second excitation light C so that the sentinel lymph node to be examined can be irradiated with the second excitation light C emitted from the laparoscope 10 is monitored. Further, the irradiation position image of the second excitation light C is displayed on the monitor by the laparoscope 10 for imaging. The irradiation position of the laparoscope 10 is adjusted so that the irradiation position of the second excitation light C on the monitor comes to the place of the sentinel lymph node S in the superimposed image in the irradiation position image. When the irradiation position is determined, it is confirmed whether or not the second fluorescence c is observed on the second fluorescence intensity monitor. Since the irradiation spot diameter of the second excitation light C is about the same as that of the sentinel lymph node, it is confirmed whether fluorescence is detected in the sentinel lymph node.

  On the other hand, when the fluorescence measuring unit 80 is a “spectrometer”, the fluorescence wavelength spectrum of the second fluorescence c guided to the spectrometer is measured by the spectrometer. As the measurement result, the waveform of the fluorescence spectrum and the numerical value of the intensity of the designated wavelength are displayed on the monitor 200. The doctor determines whether or not the second fluorescence c emitted from the second fluorescent substance is included by analyzing the display on the monitor 200. As a result of the analysis, if there is a wavelength of the second fluorescence c emitted from the second fluorescent substance, the sentinel lymph node S has the second fluorescent substance combined with cancer cells / cancer tissues. In that case, it is found that cancer cells and cancer tissues have metastasized to the sentinel lymph node S. Note that only the monitor 200 may be provided in the inspection apparatus 1, and the result of the spectral fluorescence wavelength spectrum may be displayed together with the monitor 200. Further, even when the fluorescence measuring unit 80 is a “spectrometer”, as shown in FIG. 14 and FIG. 16, an optical filter is selected and installed in front of the incident unit of the spectroscope as necessary. The wavelength spectrum can be accurately analyzed by blocking the wavelength band that becomes or transmitting only the wavelength necessary for measurement.

  From the above display steps, the inspection method according to the present invention can be used for diagnosis of metastasis of cancer cells / cancer tissues. In other words, metastasis can be diagnosed based on the results obtained in the sentinel lymph node examination step, other examination results, and the judgment of the doctor, and the treatment policy can be determined.

  The sentinel lymph nodes and cancer cells to which cancer cells / cancer tissues have metastasized by arbitrarily combining the visible light image, the first fluorescence image, the second fluorescence image, and the second fluorescence intensity measurement result The step of visualizing the position of the cancer tissue can be called a visualizing step.

(Measurement of second fluorescence intensity)
When a cancer cell / cancer tissue exists in the sentinel lymph node S, the cancer cell / cancer tissue specifically binds to the second fluorescent substance. However, the sentinel lymph node is small, and the second fluorescence emitted from the second fluorescent material specifically bound to the cancer cell / cancer tissue has a weak fluorescence intensity. Therefore, when the second excitation light C is irradiated in a range wider than the sentinel lymph node within the observation range (a range as wide as the irradiation range of the first excitation light B), the spectrum of the second fluorescence c Is likely not to be measured. For this reason, it is desirable to squeeze the second excitation light C to the same size as the sentinel lymph node S and irradiate the sentinel lymph node S.

  By irradiating the sentinel lymph node S with the second excitation light C having the same size, the second fluorescence c emitted from the second fluorescent substance specifically bound to the cancer cell / cancer tissue is selectively detected. it can. Therefore, based on the first fluorescence image, the laparoscope 10 is fixed at the position of the identified sentinel lymph node S, the second excitation light C is irradiated from the laparoscope 10, and the second position is irradiated from the irradiated position. Whether or not the fluorescence c is detected (whether or not the second fluorescence c is emitted) can be confirmed to determine whether or not the cancer cell / cancer tissue has metastasized to the sentinel lymph node S.

  According to the inspection method using the inspection apparatus 1 of the case 1 described above, the second excitation light C is irradiated to the same size as the predetermined sentinel lymph node in the observation range P, so that the diagnosis with high sensitivity and high resolution is performed. It can be performed. In addition, it is possible to accurately diagnose whether or not cancer cells / cancer tissues have metastasized, and where they have metastasized, if they have metastasized.

  For example, if no metastasis of gastric cancer, for example, is found in the sentinel lymph node with the second fluorescence c, an early gastric cancer C ′ portion having a size of about 10 mm is excised. If the gastric cancer is outside the stomach, it can be excised by laparoscopic surgery, and if it is inside the stomach, it can be excised by endoscopic surgery. After that, as described later, by applying the second excitation light C widely, when cancer cells / tissues remain, the second fluorescence c is emitted, so it is confirmed whether there is any cancer left behind. it can.

(Application of inspection method)
As an application example of the inspection method, it is also applied after excision of cancer cells / cancerous tissue of the lesion C ′ based on the metastasis information to the sentinel lymph node S provided by the above-described inspection method according to the present invention. Can do. That is, after the cancer cell / cancer tissue is excised, in order to confirm that no cancer cell / cancer tissue remains in the excised portion, the test method according to the present invention can be performed.

  That is, as a result of irradiating the portion where the lesion C ′ is excised with the second excitation light C, if the second fluorescence image or the second fluorescence intensity is detected as a result of being observed in the second fluorescence image, the lesion It can be seen that C ′ has left behind cancer cells and cancer tissues. In addition, as a result of irradiating the second excitation light B to the part where the lesioned part C ′ is excised, if the second fluorescence image cannot be observed, or if the second fluorescence spectrum or the second fluorescence intensity is not detected, the lesion It can be seen that there is no leftover of cancer cells / cancerous tissue in part C ′. Therefore, it is possible to confirm whether or not a cancer cell / cancer tissue excision operation has been performed reliably by observation and detection using this inspection method. If cancer cells / tissues remain, the portion observed in the second fluorescence image or the portion where the second fluorescence spectrum or the second fluorescence intensity is detected is removed. At this time, if the second excitation light C is widely irradiated to detect whether the second fluorescence c is shining or not shining, it is possible to confirm the leftover of cancer cells and cancer tissue in a wide range.

  Note that this application example is not limited to the one using a laparoscope, and can be performed by, for example, providing the endoscope with the same function.

  Moreover, the range observed by applying the above inspection method after excision may be expanded from the initial observation range. After excision of cancer cells / cancerous tissue, by observing the cancer cell / cancerous tissue beyond the original range, other cancer cells / cancerous tissue that may exist in the vicinity of the excised cancer cell / cancerous tissue are found, followed by It can be used as information for determining whether or not excision is effective. The inspection method according to the present invention can be effectively used as such re-inspection means.

[Inspection method / Case 2]
As described above, the inspection method using the inspection apparatus 1B of case 2 also displays the step of confirming the position of the sentinel lymph node S, the step of irradiating the second excitation light C, and the second fluorescence image. The inspection apparatus 1B of the case 2 used here has a display step and / or a display step for displaying a fluorescence spectrum. As shown in FIGS. 3 and 4, the laparoscope 10 has a first excitation light irradiation function. The first fluorescent light receiving function, the second excitation light irradiation function, and the second fluorescent light receiving function are in charge, and the laparoscope 20 is in charge of the illumination light irradiation function and the imaging function.

  Since each function is the same as that of the inspection apparatus 1A of the case 1, the description thereof is omitted here. However, the major difference is that the inspection apparatus 1B of the case 2 includes an imaging laparoscope 20 and an irradiation abdominal cavity. The point is that it also serves as a mirror.

[Inspection method / Case 3]
As described above, the inspection method in the case of using the inspection apparatus 1C of case 3 also includes the step of confirming the position of the sentinel lymph node S, the step of irradiating the second excitation light C, and the display for displaying the second fluorescence image. 5. The inspection apparatus 1C of Case 3 used here includes a step and / or a display step for displaying a fluorescence spectrum. As shown in FIG. 5, the laparoscope 10 includes an illumination light irradiation function and first excitation light irradiation. The laparoscope 20 has a first fluorescence light receiving function, a second excitation light irradiation function, and a second fluorescence light receiving function, and the laparoscope 30 has an imaging function.

  Each function is the same as that of the inspection apparatus 1A of the case 1, and thus the description thereof will be omitted here. However, the major difference is that the inspection apparatus 1C of the case 3 shares the roles of three laparoscopes. Is a point.

[Configuration of inspection equipment]
Next, the configuration of each inspection apparatus 1 (1A, 1B, 1C) shown in FIGS. 1 to 5 will be described. The inspection apparatus 1 includes illumination light irradiation means, first excitation light irradiation means, second excitation light irradiation means, image capturing means, and fluorescence measurement means. In the following, taking the inspection apparatus 1A of case 1 as an example, the laparoscope 10 functions as illumination light irradiation means, first excitation light irradiation means, second excitation light irradiation means, and fluorescence measurement means. The case where the laparoscope 20 functions as an image capturing means will be described, but the inspection device 1B of the case 2 will also be described as necessary.

  The laparoscope 10 is a means for irradiating the observation range P with the illumination light A, and a means for irradiating the observation range P with the first excitation light B (near infrared) and the second excitation light C. Further, fluorescence by fluorescence b and c emitted from one or both of the first fluorescent material for detecting lymph nodes and lymph vessels and the second fluorescent material for detecting cancer cells and cancer tissues within the observation range P. Means for guiding an image. The laparoscope 20 is a means for guiding the visible light by the visible light a reflected in the observation range P and the fluorescence b and c emitted from one or both of the first fluorescent material and the second fluorescent material to the imaging device 90. is there.

  Since the inspection apparatus 1 including the laparoscopes 10 and 20 irradiates the observation light P with the illumination light A and the first excitation light B from the laparoscope 10, for example, the visible light image of the illumination light A and the first excitation light are emitted. From the fluorescence image emitted from the first fluorescent material by the irradiation of the light B, the exact position and distribution of the sentinel lymph node S can be found in a wide range around the outside of the organ having the lesion. Then, since the second excitation light C for generating the second fluorescence c is emitted from the second fluorescent material, the second excitation light C has a size approximately equal to the size of the sentinel lymph node. By narrowing down to the spot size, the sentinel lymph node can be examined with high sensitivity and high resolution, and the examination of cancer cells and cancer tissues existing in the sentinel lymph node can be realized. Moreover, the position of the sentinel lymph node to be examined and the excitation light are obtained by irradiating the sentinel lymph node to be examined with the first excitation light B and taking a first fluorescence image generated by the first excitation light B. The irradiation position can be confirmed on the display means (monitor) 200.

(Laparoscope 10)
FIG. 6 is a cross-sectional configuration diagram illustrating an example of a laparoscope 10 </ b> A used in the inspection apparatus 1 </ b> A of case 1. As shown in FIG. 6, the laparoscope 10A includes an illumination light irradiation optical fiber 301 as illumination light irradiation means, a first excitation light irradiation optical fiber 303 as first excitation light irradiation means, The two excitation light irradiation optical fibers 302 are provided as second excitation light irradiation means, and the fluorescence receiving optical fibers 304 are provided as fluorescence measurement means.

  In the laparoscope 10A shown in FIG. 6, one optical fiber 302 for second excitation light irradiation inserted into the shield pipe 302a is disposed in an elongated cylindrical sheath tube 305. Around the second excitation light irradiation optical fiber 302, four first excitation light irradiation optical fibers 303 are arranged. A plurality of fluorescent light receiving optical fibers 304 are arranged around the second excitation light irradiation optical fiber 302 and the first excitation light irradiation optical fiber 303, and further, on the inner wall surface of the sheath tube 305 around the optical fibers 304, A plurality of illumination light irradiation optical fibers 301 are arranged. The shield pipe 302a acts to prevent the excitation light leaking from the second excitation light irradiation optical fiber 302 from affecting other optical fibers. Further, a lens or the like may be provided at the tip of the laparoscope 10A, and the spread of light can be adjusted.

  The number and arrangement of the optical fibers are not particularly limited, but it is preferable to have an arrangement relationship as shown in FIG. The sheath tube 305 may contain a filler such as a resin, and the filler is preferably an adhesive. In the example of FIG. 8, one second excitation light irradiation optical fiber 302 and four first excitation light irradiation optical fibers 303 are arranged in the center of the sheath tube 305. This is an example in which the fluorescent light receiving optical fiber 304 and the illumination light irradiating optical fiber 301 are arranged on the wall surface side, and in particular, an example in which the excitation light irradiating optical fibers 302 and 303 and the fluorescent light receiving optical fiber 304 are spaced apart. FIG.

  In the laparoscope 10A, each optical fiber is branched at a branching section (not shown). As shown in FIG. 1, the branched optical fibers are wired and connected to each other. For example, the illumination light irradiation optical fiber 301 is connected to the illumination light source 50 as the illumination light irradiation optical fiber cable 14, and the first excitation light irradiation optical fiber 303 is the first excitation light irradiation optical fiber cable 15. The first excitation light irradiation optical fiber 302 is connected to the second excitation light source 70 as the second excitation light irradiation optical fiber cable 26, and the fluorescence receiving optical fiber 304 is used for fluorescence reception. The optical fiber cable 27 is connected to the fluorescence measuring unit 80. Each optical fiber cable may have a bundle structure, be provided with a protective cover, or be fixed by a fixing means such as an adhesive.

  FIG. 9 is a cross-sectional configuration diagram illustrating an example of a laparoscope 10B used in the inspection apparatus 1B of the case 2. As shown in FIG. 9, the laparoscope 10B is an optical fiber bundle composed of a plurality of optical fibers, and includes a first excitation light irradiation optical fiber 303 as a first excitation light irradiation means, and a second excitation light irradiation means. The light irradiation optical fiber 302 is provided as second excitation light irradiation means, and the fluorescence receiving optical fiber 304 is provided as fluorescence measurement means. Unlike the inspection apparatus 1A of the case 1, the inspection apparatus 1B of the case 2 does not have the illumination light irradiation means, so the laparoscope 10B shown in FIG. 9 also includes the illumination light irradiation optical fiber 301. I don't have it. The rest of the configuration is the same as that of the laparoscope 10A.

(Laparoscope 20)
FIG. 7 is a cross-sectional configuration diagram illustrating an example of a laparoscope 20 </ b> A used in the inspection apparatus 1 </ b> A of case 1. As shown in FIG. 7, the laparoscope 20A includes an imaging optical fiber bundle 310 as an imaging unit. In the laparoscope 20A, an imaging optical fiber bundle 310 is disposed in the center of an elongated cylindrical sheath tube 313. A filler 311 is filled around the imaging optical fiber bundle 310. Such an arrangement is not particularly limited, but an arrangement relationship as shown in FIG. 7 is preferable. Although not shown, a condensing lens may be provided on the distal end side of the imaging optical fiber bundle 310. As shown in FIG. 1, the imaging optical fiber bundle is connected to the imaging device 90 as an imaging fiber cable 27.

  10 is a cross-sectional configuration diagram illustrating an example of a laparoscope 20B used in the inspection apparatus 1B of case 2. As shown in FIG. 10, the laparoscope 20B includes an imaging optical fiber bundle 310 as an image imaging means in the center of the sheath tube 313, and an illumination light irradiation optical fiber 312 as an illumination light irradiation means. 313 is provided on the inner wall surface side. Such an arrangement is not particularly limited, but an arrangement relationship as shown in FIG. 10 is preferable. Although not shown, a condensing lens may be provided on the distal end side of the imaging optical fiber bundle 310. As shown in FIG. 3, the imaging optical fiber bundle 310 is connected to the imaging device 90 as an imaging fiber cable 41, and the illumination light irradiation optical fiber 301 is connected to the illumination light source 50 as the illumination light irradiation optical fiber cable 14. Connected.

  These laparoscopes 10 and 20 are attached to a patient. As shown in FIGS. 1 to 4, the laparoscopes 10 and 20 are attached to the patient by attaching holders 11 and 21 to the laparoscopes 10 and 20 and supplying carbon dioxide to the abdomen in advance from the insertion opening H formed in the patient. It is introduced and inflated, and inserted into the laparoscopes 10 and 20 from the tip. The holders 11 and 21 are members formed in a cylindrical shape, and are inserted and disposed inside the insertion port H (inner wall portion) formed in the outer skin of the patient, and the holders 11 and 21 perform laparoscopes 10 and 20. Can be kept airtight in the insertion opening H. The center of the holders 11 and 21 has a penetrating portion extending in the axial direction, and the sheath tubes 12 and 22 are inserted into the penetrating portions and held by the holders 11 and 21.

  The distal ends of the laparoscopes 10 and 20 are preferably provided with transparent sealing portions 13 and 24 for sealing the distal ends. The transparent sealing portions 13 and 24 are made of a transparent member such as glass or plastic film, and are used to observe the illumination light A and the first excitation light B (near infrared) emitted from the tip of the optical fiber. A wide range including P can be irradiated, and visible light a, first fluorescence b, and second fluorescence c can be received.

  In the inspection apparatus 1A of case 1, as shown in FIG. 1, the laparoscope 10 irradiates the wide observation range P with the illumination light A and the first excitation light B. The “observation range P” here is a range in which the first fluorescent material for detecting the sentinel lymph node is observed. As shown in FIG. 1, by irradiating illumination light A and first excitation light B to a wide observation range P, the built-in surface Q can be easily observed using an imaging laparoscope 20, and illumination light can be observed. The influence of the intensity distribution of A can also be reduced, and the received light intensity can be made uniform in the observation range P for imaging.

  In order to irradiate a wide observation range P, the tip structure of the laparoscope 10 is arbitrarily designed. Only the transparent sealing portion 13 may be provided at the distal end of the laparoscope 10, or the transparent sealing portion 13 may be provided at the distal end of the laparoscope 10, and a lens may be provided between the distal end and the transparent sealing portion 13. (Not shown) may be provided.

  On the other hand, in the inspection apparatus 1B of the case 2, as shown in FIG. 3, the laparoscope 10 irradiates the first excitation light B to the wide observation range P, and the laparoscope 20 illuminates the illumination light A to the wide observation range P. Irradiate. As shown in FIG. 3, by irradiating the first observation light B and the illumination light A to the wide observation range P by the laparoscopes 10 and 20, the built-in surface Q is formed using the imaging laparoscope 20. In addition to being able to observe easily, the influence of the intensity distribution of the illumination light A can be reduced, and the received light intensity can be made uniform in the observation range P for imaging. In addition, the transparent sealing part 13 and a lens are the same as that of said case.

(Function of imaging laparoscope)
As shown in FIGS. 1 to 4, the imaging laparoscope 20 has illumination light A irradiated from the laparoscope 10 (case 1 inspection device) or laparoscope 20 (case 2 inspection device) in the observation range P. Reflected visible light a, excited by first excitation light B emitted from laparoscope 10 (inspection apparatus of cases 1 and 2), and first fluorescence for detecting lymph nodes and lymphatic vessels within observation range P By the first fluorescence b emitted from the substance and the second excitation light C irradiated from the laparoscope 10 (inspection apparatus of cases 1 and 2) to the same size as a specific sentinel lymph node within the observation range P It is an image transmission means for guiding and imaging one or more light of the second fluorescence c emitted from the second fluorescent material for detecting cancer cells / cancer tissues when excited. .

  The imaging laparoscope 20 is connected to the imaging device 90 via the optical fiber cable 41. The imaging device 90 uses the guided visible light a as a visible light image, and the first guided light. Fluorescent b is used as the first fluorescent image, and the guided second fluorescent c is used as the second fluorescent image. By using the visualized visible light image and the first fluorescent image, it is possible to detect the exact position and distribution of the sentinel lymph node in a wide range around the lesion C ′. In addition, the second fluorescence image obtained by imaging the second fluorescence c emitted from the second fluorescent substance is photographed to display the position of the specific sentinel lymph node to be examined and the irradiation position of the excitation light. It can be confirmed on the means (monitor).

(Imaging device)
The imaging device 90 is connected to the imaging laparoscope 20 and images the visible light a guided to the imaging laparoscope 20 to form a visible light image, while being guided to the laparoscope 20. The first fluorescence b can be imaged to be a first fluorescence image, and the second fluorescence c guided to the laparoscope 20 can be imaged to be a second fluorescence image.

  Specifically, as shown in FIGS. 11 and 12, a housing 91 that forms an outer shell, a dichroic mirror 92 (also referred to as a light separating unit 92) that is a light separating unit provided inside the housing 91, and A CCD camera 93 that captures light separated by the dichroic mirror 92 and a near-infrared CCD camera 94 that captures fluorescence are provided.

  The light separating unit 92 separates the visible light a and the fluorescence (first fluorescence b, second fluorescence c) guided by the optical fiber bundle 41 extending from the laparoscope 20 and is connected to the image processing unit 110. Yes. Specifically, the dichroic mirror 92 is disposed obliquely with respect to the traveling direction of the visible light a and the fluorescent light b and c that are guided through the optical fiber cable 41. The dichroic mirror 92 acts to transmit visible light as it is and to reflect without transmitting fluorescence.

(control)
In the inspection apparatus 1A of the case 1, the laparoscope 10 is connected to the illumination light source 50 via the illumination light irradiation optical fiber cable 14 and via the first excitation light irradiation optical fiber cable 15 as shown in FIG. Connected to the first excitation light source 60, connected to the second excitation light source 70 via the second excitation light irradiation optical fiber cable 26, and connected to the fluorescence measuring unit 80 via the fluorescence receiving optical fiber cable 27. Yes. The illumination light irradiation optical fiber cable 14 guides the illumination light A emitted from the illumination light source 50 to the tip of the laparoscope 10, and the first excitation light irradiation optical fiber cable 15 emits the first excitation light source 60. The second excitation light irradiation optical fiber cable 26 guides the second excitation light C emitted from the second excitation light source 70 to the distal end of the laparoscope 10. .

  The illumination light source 50 is not particularly limited as long as it is a light source that emits illumination light A. For example, a lamp that emits white light, such as a halogen lamp, a mercury lamp, or a white LED, or a lamp that emits visible light can be used.

  The first excitation light source 60 is not particularly limited as long as it is a light source that emits the first excitation light B, but a light source that emits near infrared light having a wavelength of 700 nm to 830 nm is preferable. When a halogen lamp or a mercury lamp is used as the first excitation light source 60, it is preferable to cut and use a wavelength of less than 700 nm. Further, an LED light source or a laser light source having a wavelength band of 700 nm to 830 nm may be used.

  The second excitation light source 70 includes a semiconductor laser that emits laser light and a driver that turns on and off the semiconductor laser. As the excitation light of the second excitation light source 70, although it depends on the type of fluorescent material to be emitted, it is preferable to use laser light having a wavelength of 400 to 1300 nm, and more preferably, laser light having a wavelength of 600 to 1100 nm. Select according to the fluorescent substance to be used.

  Control of the laparoscope 10 is performed by the control device 100. The control device 100 includes a timing control unit 150 that controls the timing of the illumination light A and the first excitation light B in the above-described position observation step. The timing control unit 150 is connected to the illumination light source 50 and the first excitation light source 60, and further connected to a second excitation light source 70, which will be described later, to control turning on and off of the illumination light source 50, and turning on the first excitation light source 60. And the turning on and off of the second excitation light source 70 to be described later. The illumination light source 50, the first excitation light source 60, and the second excitation light source 70 are associated with each other and the timing is controlled. The timing may be controlled by a method in which a shutter that blocks light is provided and the shutter is opened and closed to control the timing.

  The timing processing unit 150 (a) appropriately switches the light source to be irradiated, irradiates the observation range P with the illumination light A, acquires a visible light image of the observation range P, and inspects the whole (b). Irradiating the observation range P with the first excitation light B, acquiring a first fluorescent image based on the first fluorescent substance, and specifying a location where the first fluorescent substance is contained; (c ) Synthesize the visible light image and the first fluorescent image to inspect the position of the lymphatic vessel or sentinel lymph node, (d) add the second fluorescent substance to a predetermined site (sentinel lymph node) in the observation range P By irradiating the second excitation light C to be excited, the second fluorescence c is generated, and it is possible to inspect whether there is a cancer cell / cancer tissue to which the second fluorescent substance is bound. . These test results and other test results are combined to determine a treatment policy.

  When only the illumination light A is irradiated to the observation range P, only the illumination light source 50 is turned on, the first excitation light source 60 is turned off, and the driver of the second excitation light source 70 described later is turned off. When only the first excitation light B is irradiated to the observation range P, only the first excitation light source 60 is turned on, the illumination light source 50 is turned off, and the driver of the second excitation light source 70 described later is turned off. To do. When the observation range P is irradiated with both the illumination light A and the first excitation light B, both the illumination light source 50 and the first excitation light source 60 are turned on, and a driver for the second excitation light source 70 described later is turned on. Turn off. When the first excitation light B is irradiated to the observation range P and the second excitation light C is irradiated to a predetermined sentinel lymph node in the observation range P, the first excitation light source 60 is turned on. The driver of the second excitation light source 70 is turned on and the illumination light source 50 is controlled to be turned off. In addition, when irradiating only the 2nd excitation light C mentioned later to the predetermined sentinel lymph node of the observation range P, the illumination light source 50 and the 1st excitation light source 60 are turned off, and the driver of the 2nd excitation light source 70 is turned ON. To. ON and OFF of these light sources are controlled in association with each other, and the control is performed by providing a shutter and controlling the timing for opening and closing the shutter.

  The timing control unit 150 is connected to a superimposed image processing unit 140 of the image processing unit 110 described later, and selects the type of image to be displayed on the monitor 200 in association with irradiation of illumination light, near infrared light, and excitation light. Is controlling. Details of display control on the monitor 200 will be described later.

(Image processing unit)
The image processing unit 110 performs image processing for imaging the received visible light, fluorescence, and the like. As shown in FIGS. 11 and 12, the image processing unit 110 includes a visible light image processing unit 120, a fluorescence image processing unit 130, and a superimposed image processing unit 140, and further includes an image switching unit (not shown). Yes.

  The visible light image processing unit 120 is a processing unit for imaging visible light into a visible light image. Specifically, the visible light image processing unit 120 is a processing unit for capturing the visible light separated by the light separating unit 92 with the CCD camera 93 and projecting the visible light image obtained by imaging the visible light on the monitor 200. . The visible light image processing unit 120 is connected to a CCD camera 93 provided in the housing 91 of the imaging device 90 and captures and visualizes the visible light (the reflected illumination light) captured by the CCD camera 93. Thus, a visible light image (color image or the like) is obtained.

  The fluorescence image processing unit 130 is a processing unit for imaging fluorescence (mainly first fluorescence) into a fluorescence image (mainly first fluorescence image). Specifically, it is a processing unit for capturing the fluorescence separated by the light separating means 92 with the near-infrared CCD camera 94 and projecting the fluorescence image obtained by imaging the fluorescence on the monitor 200. The fluorescence image processing unit 130 is connected to a near-infrared CCD camera 94 provided in the housing 91 of the imaging device 90, and fluorescence captured by the near-infrared CCD camera 94 (fluorescence emitted from the first fluorescent material). Is captured and imaged to obtain a fluorescent image.

  The superimposed image processing unit 140 can display a superimposed image obtained by superimposing the visible light image obtained by the visible light image processing unit 120 and the fluorescent image obtained by the fluorescent image processing unit 130 on the monitor 200. A processing unit for processing. In the process of superimposing the image, the irradiation position of the second excitation light C that excites the second fluorescent substance (that is, the position of a specific sentinel lymph node) may be superimposed on the visible light image, the fluorescent image, or the superimposed image. The same process can be performed.

  The superimposed image processing unit 140 is connected to the timing control unit 150 described above. Therefore, selection of an image to be displayed on the monitor 200 is associated with the irradiation timing of the illumination light A, the first excitation light B, and the second excitation light C controlled by the timing processing unit 150.

  Examples of control of the timing processing unit 150 for displaying an arbitrary image on the monitor 200 include the following examples. For example, (1) when the illumination light source 50, the first excitation light source 60, and the second excitation light source 70 are controlled so as to irradiate only the illumination light A to the observation range P, the monitor 200 receives visible light a. An imaged visible light image is displayed. (2) When the illumination light source 50, the first excitation light source 60, and the second excitation light source 70 are controlled so as to irradiate only the first excitation light B to the observation range P, the monitor 200 includes A first fluorescence image obtained by imaging the first fluorescence b emitted from one fluorescent material is displayed. (3) When the illumination light source 50, the first excitation light source 60, and the second excitation light source 70 are controlled so that only the second excitation light C is irradiated to a predetermined sentinel lymph node within the observation range P The monitor 200 displays a second fluorescent image obtained by imaging the second fluorescent light c emitted from the second fluorescent material.

  On the other hand, (4) the illumination light source 50 and the first excitation light B are irradiated so that the illumination light A and the first excitation light B are irradiated simultaneously or alternately, but the second excitation light C is not irradiated. When the light source 60 and the second excitation light source 70 are controlled, the monitor 200 displays the visible light image and the first fluorescent image in a superimposed manner. (5) The illumination light source 50, the first excitation light source 60, and the second excitation light source 70 are controlled so that the second excitation light C is irradiated but the illumination light A and the first excitation light B are not irradiated. If it is, the monitor 200 displays the visible light image, the first fluorescent image, and the second fluorescent image that are captured in advance in a superimposed manner. The display of images on the monitor 200 can select each image alone, two selected images, or all three superimposed images. (6) When the wavelength spectrum is measured using the fluorescence measuring unit 80, the observation range P is irradiated because the second fluorescent substance specifically bound to a specific sentinel lymph node is very small. Since the illumination light becomes noise, it is preferable to turn off the illumination light source 50 and the first excitation light source 60 to detect the second fluorescence.

  In the inspection apparatus 1, an automatic mode in which an image to be displayed on the monitor 200 is automatically switched in association with the timing of irradiating the illumination light A, the first excitation light B, and the second excitation light C irradiating the observation range P. Switching means may be provided, or manual mode switching means manually switched by the doctor may be provided. The switching means in the manual mode can freely select the type of image to be displayed on the monitor 200 based on the judgment of the doctor.

  In addition, when the 2nd excitation light C irradiated in order to make the 2nd fluorescence c light-emit from a 2nd fluorescent substance is the wavelength range of a near infrared light to an infrared light, the light is used for a near infrared CCD camera. It is also possible to measure and image the image and to further superimpose it on a superimposed image obtained by superimposing the visible light image and the fluorescence image. In addition, when the second excitation light C irradiated to emit the second fluorescence c from the second fluorescent substance is in the visible light wavelength range, the light is measured with a CCD camera and imaged. You may further superimpose on the superimposition image which overlap | superposed the visible light image and fluorescence image which were performed. By performing these superpositions, it is possible to confirm whether or not the second excitation light C is irradiated to the target location (sentinel lymph node).

  The image switching unit (not shown) is a processing unit for selectively displaying a visible light image, a fluorescent image, or a superimposed image on the monitor 200. The captured image and the image after image processing can be recorded on a recording device (not shown), and can also be displayed on the monitor 200 using the image recorded on the recording device.

  As shown in FIGS. 11 and 12, the CCD camera 93 that captures the visible light A is located on a straight line connecting the emission end of the imaging laparoscope 20 and the center of the dichroic mirror 92, and is located behind the dichroic mirror 92. The lens is set toward the dichroic mirror 92. On the other hand, as shown in FIGS. 11 and 12, the near-infrared CCD camera 94 for imaging fluorescence is at a position orthogonal to a straight line connecting the emission end of the imaging laparoscope 20 and the center of the dichroic mirror 92 and is dichroic. It is provided at a position on the side of the mirror 92, and the lens is set toward the dichroic mirror 92. The imaging device 90 including these CCD cameras 93 and 94 includes a near-infrared CCD camera 94 and a dichroic mirror 92 so that only the fluorescence is captured by the near-infrared CCD camera 94 by cutting visible light and reflected excitation light. A first filter 95 is attached between the two.

  Further, the imaging device 90 is provided with a second filter 96 that transmits only the first fluorescence b emitted from the first fluorescent material to the near-infrared CCD camera 94, and the second filter 96 is disposed in front of the lens. The imaging device 90 can be configured to be detachable. Since the second filter 96 cuts off the fluorescence emitted by the fluorescent material other than the first fluorescent material, the near-infrared CCD camera 94 can image only the first fluorescence b emitted by the first fluorescent material. Further, when the type of the first fluorescent material is changed, it can be used for other fluorescent materials (substances having different fluorescence wavelength bands) by simply replacing the detachable second filter 96.

  In the imaging device 90 configured in this way, the visible light a received by the imaging laparoscope 20 is transmitted through the dichroic mirror 92 and guided to the CCD camera 93. The CCD camera 93 images the guided visible light to form an image, and supplies the imaged image to the image processing unit 110. On the other hand, the fluorescences a and b received by the imaging laparoscope 20 are reflected in a direction perpendicular to the approach direction to the dichroic mirror 92 and guided to the near-infrared CCD camera 94.

  When the near-infrared CCD camera 94 images the first fluorescence b, a near-infrared cut filter for separating the first fluorescence b and the reflected near-infrared light by attaching a second filter 96 in front of the lens. The reflected near infrared rays are cut by the second filter 96, and only the first fluorescence b is guided to the near infrared CCD camera 94.

  In addition, when irradiating a specific sentinel lymph node to which a second fluorescent substance is specifically bound from a laparoscope 20 to be described later with the second excitation light C and imaging the irradiation position, the second irradiation light is irradiated. The illumination light irradiation CCD camera 93 or the near-infrared CCD camera 94 is selected and used in accordance with the wavelength of the excitation light C or the wavelength of the second fluorescence c. Since the applicable wavelength of the second excitation light C and the wavelength of the second fluorescence c are determined by selecting the second fluorescent material, the wavelength of the second excitation light C and the wavelength of the second fluorescence c are determined. The wavelength characteristics of the dichroic mirror 92 and the filters 95 and 96 are selected corresponding to the above. On the other hand, when imaging the second fluorescence c emitted from the second fluorescent material, the second filter 96 in front of the lens is replaced with filters 95 and 96 adapted to the second fluorescence c. The near-infrared CCD camera 94 captures and images the guided second fluorescence c, and supplies the image to the image processing unit 110. When the second fluorescent light c is visible light, a filter suitable for the second fluorescent light c is provided in front of the CCD camera 93 (it may be detachable or switchable), or visible at the position of the near infrared CCD 94. For example, a light CCD is provided.

  FIG. 14 shows an imaging apparatus 500 (imaging apparatus 90 in FIG. 14) that is preferably used when the second excitation light C is visible light and the wavelength of the second excitation light C is close to the wavelength of the second fluorescence c. Is indicated by the reference numeral 500). An imaging optical fiber cable 501 (the cable 41 is indicated by reference numeral 501 in FIG. 14) is connected to the imaging apparatus 500 shown in FIG. Visible light a, first excitation light B, second excitation light C, first fluorescence b, and second fluorescence c are guided from the connector unit 502 into the imaging apparatus 500. Each of the guided light is magnified by the collimator lens 503 and reaches the dichroic mirror 508. Since the dichroic mirror 508 transmits the visible light wavelength, the visible light a in the visible light region and the second excitation light C are transmitted. Of the transmitted visible light a and second excitation light C, the second excitation light C is cut by the optical filter 507, the visible light a is condensed by the collimator lens 506, and captured by the visible light image capturing device 510. Is done. On the other hand, near-infrared rays (first excitation light B, first fluorescence b) reflected by the dichroic mirror 508 pass through the optical filter 509 that cuts the first excitation light B, and are collected by the collimator lens 503. An image is picked up by the imaging device 504 of the imaging device for near infrared rays (first fluorescence b).

  According to the imaging device 90 (500) described above, the entire state of the observation range P can be grasped in detail by displaying the visible light image obtained by imaging the visible light a on the monitor 200. Further, a place where the first fluorescent substance is contained is displayed on the monitor 200 by displaying a fluorescent image obtained by imaging the first fluorescent light b emitted from the first fluorescent substance by the irradiation of the first excitation light B. Can be accurately identified. Then, the position of the sentinel lymph node is specified by the fluorescence image based on the first fluorescence b, and the second fluorescence c is emitted from the second fluorescent material to the sentinel lymph node located in the vicinity of the lesioned part C ′. By irradiating the second excitation light C to the same size as the sentinel lymph node S and irradiating it with high-density energy, the emitted second fluorescence c can be detected, and the second fluorescent substance is bound. The presence of a substance (a substance that specifically binds to cancer cells or cancer tissue) can be detected.

  Furthermore, the light received by the imaging laparoscope 20 is imaged by the imaging device 90 (500), so that the visible light image showing the irradiation range of the illumination light A and the second excitation light C are emitted. Second fluorescent light b (measurement is possible when the concentration of the second fluorescent material is relatively high. Depending on the wavelength of the second fluorescent light b, the illumination light irradiation CCD camera 93 or the near infrared CCD camera 94 is selected. And the second fluorescent image obtained from the above can be displayed on the monitor 200 as a superimposed image. As a result, the irradiation range of the illumination light A and the position of the sentinel lymph node can be confirmed with an image. As a result, the time for identifying the sentinel lymph node can be shortened, and the operation time can be shortened.

(Measurement result display controller)
The measurement result display control unit 160 is connected to a fluorescence measurement unit 80 that measures the intensity and spectrum of the second fluorescence c received by the laparoscope 10, and the measurement result obtained by the fluorescence measurement unit 80 is displayed on the monitor 200. Control the display. A fluorescence receiving optical fiber 27 is connected to the fluorescence measuring unit 80.

  The fluorescence measuring unit 80 is preferably a fluorescence detector that detects only fluorescence having a desired wavelength set in advance. As such a fluorescence detector, an optical filter that transmits a desired fluorescence wavelength or wavelength band is preferable. Specifically, an optical filter that cuts off reflected excitation light and transmits only received fluorescence is used. It is preferable. When the first fluorescence b and the second fluorescence c are measured by the fluorescence measuring unit 80, an optical means (light separation means) for separating the first fluorescence b and the second fluorescence c is provided. It is preferable to measure the fluorescence intensity independently by providing separate detectors capable of detecting each fluorescence.

  Thus, since the fluorescence measuring unit 80 includes a fluorescence detector that detects fluorescence of a preset wavelength, an optical filter that transmits the fluorescence wavelength or wavelength band of the fluorescent substance to be used is used as the fluorescence detector. If used, for example, only the second fluorescent wavelength emitted by the second fluorescent substance that specifically binds to cancer cells / cancer tissues (or the second fluorescent substance that binds specifically to cancer cells / cancer tissues) is detected. can do. As a result, by combining the fluorescence measurement results obtained in this way and the images already obtained, it is possible to check whether cancer cells / cancer tissues are present in the specified sentinel lymph nodes (ie, there is metastasis). Can be done on the spot.

  When the second fluorescent material is present in the sentinel lymph node S, the second fluorescent material emits second fluorescence having a specific wavelength. The fluorescence detector detects only the second fluorescence emitted from the second fluorescent material in which the wavelength of the second fluorescence to be detected is set in advance and the second fluorescent material present in the sentinel lymph node S. As a result, even if fluorescence having a wavelength different from that of the second fluorescent substance specifically bound to the cancer cell / cancer tissue is emitted in the sentinel lymph node S, such fluorescence is not detected, and the cancer cell / cancer tissue is detected. Only the second fluorescence from the second fluorescent substance specifically bound to can be detected accurately to determine whether the cancer cell / cancer tissue is in the sentinel lymph node S or not. When the inspection is performed by changing the type of the second fluorescent material, the filter built in the fluorescence detection unit is replaced.

  Further, the fluorescence measuring unit 80 may include a spectroscope that separates the fluorescence guided by the fluorescence receiving optical fiber cable 27 into a preset range. The spectroscope can measure the detected fluorescence as a temporal change in the wavelength spectrum distribution of the fluorescence. As a result, by analyzing the wavelength spectrum of the dispersed fluorescence, it is possible to identify which fluorescent material is emitted by the fluorescence guided to the spectrometer, and the binding state of the fluorescent material, or noise component Can be identified and analyzed. Even when a spectroscope is used, an optical filter can be selected and installed in front of the incident part of the spectroscope as necessary to cut off the wavelength band that causes noise or transmit only the wavelength necessary for measurement. This makes it possible to accurately analyze the wavelength spectrum. This filter is preferably switchable in accordance with the fluorescent reagent to be used and the second excitation light and second fluorescence corresponding thereto. The inspection apparatus 1 having such a spectroscope emits a second fluorescent material that specifically binds to cancer cells / cancer tissues (or a second fluorescent material that binds to substances that specifically bind to cancer cells / cancer tissues). Therefore, it is effective in diagnosing whether cancer is present at the position of the specified sentinel lymph node (whether there is metastasis).

  When the second fluorescent substance combined with the cancer cell / cancer tissue is present in the sentinel lymph node S, the second fluorescent substance emits fluorescence having a wavelength corresponding to the second fluorescent substance. The spectroscope measures the wavelength spectrum of the captured fluorescence. The presence of the second fluorescent material can be specified by comparing the wavelength spectrum measured by the spectroscope with the fluorescence wavelength spectrum of the second fluorescent material. That is, it is possible to identify whether the second fluorescent material combined with the cancer cells / cancer tissues present in the sentinel lymph node S emits fluorescence or other fluorescent material emits fluorescence.

(Measurement result display controller)
When the fluorescence measuring unit 80 applies an optical filter as a fluorescence detector, the measurement result display control unit 160 informs the monitor 200 that the fluorescence detector has detected the second fluorescence c emitted from the second fluorescent material. Control to display.

  On the other hand, when the fluorescence measuring unit 80 applies a spectroscope as a fluorescence detector, the measurement result display control unit 160 displays the spectral results of the divided wavelengths on the monitor 200. The display on the monitor 200 displays the fluorescence intensity numerically for each wavelength and displays a graph for each wavelength based on the digitized fluorescence intensity. The doctor determines whether or not the second fluorescence emitted from the second fluorescent material is detected by analyzing the numerical value and the graph displayed on the monitor 200.

  The fluorescence measurement unit 80 is connected to the measurement result display control unit 160 of the control device 100. When the fluorescence measurement unit 80 detects fluorescence from the second fluorescent material, a command from the measurement result display control unit 160 is received. The detection result is displayed on the monitor 200 based on the above. In this inspection apparatus 1, the monitor 200 for displaying the detection result is provided separately from the image display monitor 200. However, only the monitor 200 is provided, and the detection result is displayed on the monitor 200. Also good.

  FIG. 15 is an explanatory diagram illustrating an example of the fluorescence measurement unit, and FIG. 16 is an explanatory diagram illustrating another example of the fluorescence measurement unit. Similarly to the imaging apparatus shown in FIG. 14, the fluorescence measuring unit is preferably cut by an optical filter because the intensity of the received excitation light (first excitation light B, second excitation light C) is large. Since the received light intensity of the fluorescence (first fluorescence b, second fluorescence c) is as small as 1/1000 to 1 / 10,000 of the received excitation light, it is cut with an optical filter to measure fluorescence with high sensitivity. There is a need to.

  FIG. 15 shows a fluorescence measuring unit equipped with a CCD spectrometer capable of measuring from visible light to near infrared (in FIG. 15, the fluorescence measuring unit 80 is indicated by a CCD spectrometer 523). In this CCD spectroscope, the intensity of the light separated by the diffraction grating can be measured by a linear or planar light receiving element such as a CCD element. The position of each element corresponds to the wavelength, and the received light intensity of each wavelength can be measured simultaneously.

  FIG. 16 shows a case where light in which excitation light (first excitation light B, second excitation light C) and fluorescence (first fluorescence b, second fluorescence c) are mixed is a light-receiving optical fiber cable 531 (FIG. 16). 16, the cable 27 is guided by the reference numeral 531), and the optical fiber cable 531 for receiving light is passed through the connector part 532 to the fluorescence measuring part 550 (in FIG. 16, the fluorescence measuring part 80 is indicated by the reference numeral 550). It is connected. Excitation light and fluorescence are guided from the connector unit 532 into the fluorescence measurement unit 550. Excitation light and fluorescence are magnified by the collimator lens 535 and reach the dichroic mirror 536, and visible light components of the excitation light and fluorescence pass through the dichroic mirror 536. Of the visible light that has passed, the second excitation light C is cut by the optical filter 537 that can cut the second excitation light C having a high intensity, and the first fluorescence b is measured by the fluorescence measurement unit 534. On the other hand, of the light reflected by the dichroic mirror 536, the first excitation light B is cut by the optical filter 539 capable of cutting near-infrared light having a high intensity, and the second fluorescence c is measured by the fluorescence measuring unit 533.

  As shown in the fluorescence measurement section of FIGS. 15 and 16, the wavelengths of the excitation light (first excitation light B, second excitation light C) and fluorescence (first fluorescence b, second fluorescence c) are different. If they are close, the first fluorescent light b and the second fluorescent light c to be obtained can be received and imaged by using an optical filter capable of cutting a specific wavelength.

(monitor)
The monitor 200 is a monitor that displays an image of the observation range P, and the first fluorescence of the first fluorescent material that emits light by irradiation of the visible light image and the first excitation light B by a display mode selection switch (not shown). Each of the image and the second fluorescent image of the second fluorescent material that emits light by irradiation with the second excitation light C can be displayed independently. The monitor 200 displays a superimposed image obtained by superimposing the visible light image and the first fluorescent image by a display mode selection switch (not shown), or visible light obtained by irradiating the superimposed image with the second excitation light C. A superimposed image obtained by further superimposing the light image can be displayed, and a superimposed image obtained by further superimposing the fluorescence image excited by the second excitation light C can be displayed. Such superimposed images can be subjected to image processing for making each image easy to see on the monitor 200. Each image may be stored in a recording device (not shown), or the stored image may be displayed on the monitor 200 or another monitor.

  The monitor 200 is a monitor that displays the measurement result of the fluorescence measurement unit 80, and can display the measurement result of the fluorescence intensity and the measurement result of the fluorescence spectrum.

  As described above, the inspection apparatus 1 according to the present invention (a) irradiates the illumination light A, displays the lesion due to cancer on the monitor, (b) irradiates the first excitation light B, The first fluorescent material contained in the sentinel lymph node is caused to emit light to display the sentinel lymph node on the monitor, and (c) the second excitation light C is the same size as the sentinel lymph node S in the identified sentinel lymph node. The second fluorescent substance specifically bound to the cancer cell / cancer tissue (or the second fluorescent substance that binds to the substance specifically bound to the cancer cell / cancer tissue) emits light, and the laparoscope is highly sensitive. By using a spectroscope for the detection unit that can detect the wavelength, the wavelength spectrum of the second fluorescence c can be measured, and the wavelength spectrum of the fluorescent substance can be determined. Further, (d) the irradiation position of the second excitation light C and the second fluorescence (measurement is possible when the concentration of the second fluorescent substance is relatively high) are displayed on the monitor by the laparoscope for imaging. The irradiation position of the second excitation light C and the position of the sentinel lymph node can be confirmed with an image. Therefore, the inspection apparatus 1 according to the present invention is a suitable inspection apparatus for inspecting metastasis of cancer cells / cancer tissues.

<Inspection>
When diagnosing whether or not a patient has cancer metastasis using the inspection apparatus 1, a second fluorescent substance, which is a reagent that specifically binds to cancer cells / cancer tissues, is administered to the patient in advance. When there is metastasis of cancer, cancer cells / cancerous tissue exists in the sentinel lymph node S, and the second fluorescent substance administered to the patient is specific to the cancer cells / cancerous tissue present in the sentinel lymph node S. Are connected. When the cancer cell / cancer tissue specifically bound to the second fluorescent substance is irradiated with excitation light, the second fluorescent substance is excited and emits fluorescence.

  The inspection apparatus 1 uses the visible light image obtained by irradiating the illumination light A in advance and the first fluorescent image obtained by irradiating the first excitation light B, and uses the sentinel lymph node S in the vicinity of the lesion. And the second excitation light C is irradiated only to the sentinel lymph node S. As a result, the second fluorescence c from only the identified sentinel lymph node can be detected, and can be distinguished from the second fluorescence c from cancer cells / cancerous tissues in a lesion or the like.

  Further, since the irradiation position of the first excitation light B can be confirmed on the monitor 200 by the convolution image of the obtained visible light image and the first fluorescent image, it can be determined even if the irradiation position is deviated. The sentinel lymph nodes specified above can be irradiated. As a result, the second fluorescence c generated at the site of the sentinel lymph node can be examined.

  In the inspection apparatus 1, the second excitation light C is irradiated in a range equivalent to the sentinel lymph node S that is a predetermined sentinel lymph node existing in the observation range P or the same size as the predetermined sentinel lymph node. The second fluorescent material can be irradiated with the second excitation light C having high intensity. Therefore, even if the amount of the second fluorescent substance contained in the predetermined sentinel lymph node in the observation range P is very small, the second fluorescent substance c is surely emitted from the second fluorescent substance, The position of the specifically bound cancer cell / cancer tissue can be accurately identified. This makes it possible to examine cancer cells / cancerous tissue present in the sentinel lymph node.

  In addition, since the second excitation light C is narrowed down, even if there are cancer cells and cancer tissues nearby, they are not easily affected and the accuracy of the examination can be greatly improved. As a result, the sentinel lymph node S can be examined with high sensitivity and high resolution. Then, by narrowing the outer diameter of the second excitation light C irradiated from the sentinel lymph node S to the same level as that of the sentinel lymph node S, it is possible to greatly reduce the influence of cancer cells and cancer tissues in other parts.

  The range observed by illuminating the illumination light A with the laparoscope 10 is a wide range including an organ with a lesion C ′ caused by cancer. First, the sentinel lymph node S around the lesion is identified from such a wide range. In order to specify the sentinel lymph node S itself, the inspection apparatus 1 of the present invention irradiates the observation range P with the first excitation light B using the first excitation light source 60. The patient is preliminarily administered with a first fluorescent substance that emits light when irradiated with the first excitation light B, or is injected into a lesioned part on the spot. For example, when indocyanine green is administered to a patient as the first fluorescent substance, when indocyanine green is irradiated with near infrared light having a wavelength of 700 to 830 nm as the first excitation light B, the indocyanine green has a wavelength of Emits fluorescence b of 830 to 850 nm. Then, the light is separated using an optical filter that transmits fluorescence having a wavelength of 830 to 850 nm, and is detected by a detector.

  If the first excitation light B is irradiated to the observation range P, the position of the lymph vessel or lymph node can be monitored with a fluorescent image. By taking a fluorescent image and a visible light image alternately to create a tatami-fold image, the positional relationship between the lesioned part, lymphatic vessels, and lymph nodes can be understood from the tatami-fold image. As a result, the doctor can identify the sentinel lymph node S, which has a special effect. From the specification of the lesioned part to the specification of the sentinel lymph node can be performed in a short time with only the inspection apparatus 1 of the present invention.

  In the inspection apparatus 1 and the inspection method according to the present invention, an illumination light source 50, a first excitation light source 60, and a second excitation light source 70 are connected to the laparoscope 10, and a predetermined sentinel lymph node in the observation range P is connected to the laparoscope 20. Various features are provided on the basis of providing a diaphragm means for irradiating the second excitation light C with the same range or the same size as a predetermined sentinel lymph node.

1, 1A, 1B, 1C Inspection apparatus 10, 10A, 10A ′, 10B Laparoscope 11 Holder for patient attachment 12 Sheath tube 13 Transparent sealing portion 14 Optical fiber cable for illumination light irradiation 15 Optical fiber for first excitation light irradiation Cable 20, 20A, 20B Laparoscope 21 Holder for patient attachment 22 Sheath tube 24 Transparent sealing part 26 Optical fiber cable for second excitation light irradiation 27 Optical fiber cable for fluorescence reception 29 Branch part 30 Imaging laparoscope 31 Patient attachment Holder 32 sheath tube 33 transparent sealing portion 34 magnifying means 341 lens 35 relay lens system 351 lens 41 optical fiber cable for imaging 50 illumination light source 60 first excitation light source 70 second excitation light source 80 fluorescence measurement unit 90 imaging device 91 housing 91A Connector 92 Dichroic mirror Light separation means)
93 CCD camera 94 Near-infrared CCD camera 95 First filter 96 Second filter 100 Control device 110 Image processing unit 120 Visible light image processing unit 130 Fluorescent image processing unit 140 Superimposed image processing unit 150 Timing control unit 160 Measurement result display control unit 200 Monitor 301 Illuminating light irradiation optical fiber 302 Second excitation light irradiation optical fiber 302a Shield pipe 303 First excitation light irradiation optical fiber 303a Shield pipe 304 Fluorescent light receiving optical fiber 305 Sheath tube 306 Filler 310 Imaging optical fiber 311 Filler 312 Illuminating light irradiation optical fiber 313 Sheath tube 500 Imaging device 501 Imaging optical fiber cable 502 Connector portion 503 Collimator lens 504 Near infrared imaging device 505 Near infrared 506 Collimating lens 507 Second excitation light cutting optical filter 508 Dichroic mirror 509 First excitation light cutting optical filter 510 Imaging device for visible light image 521 Fluorescent light receiving optical fiber cable 522 Connector portion 523 CCD spectrometer 531 Fluorescent light receiving optical fiber Cable 532 Connector unit 533 First fluorescence measuring device 534 Second fluorescence measuring device 535 Collimating lens 536 Dichroic mirror 537 Optical filter 538 Collimating lens 539 Optical filter 550 Fluorescence measuring unit

A Illuminating light a Visible light B First excitation light b First fluorescence C Second excitation light c Second fluorescence H Laparoscope insertion port P Observation range Q Visceral surface
S, S1, S2, S3 Sentinel lymph node R lymphatic vessel C 'lesion (cancer)

Claims (4)

Using two laparoscopic, there is provided an inspection apparatus for providing information for determining the metastasis of cancer cells or cancer tissue into sentinel lymph node within the observation range,
A first laparoscope of the laparoscopes includes the following image capturing means (D),
Among the laparoscopes, a second laparoscope includes the following illumination light irradiation means (A), the following first excitation light irradiation means (B), and the following second excitation light irradiation means (C). An inspection apparatus using a laparoscope , comprising the first and second fluorescence measuring means (E) .
(A) Illumination light irradiation means for irradiating the observation range with illumination light;
(B) a first excitation light irradiation means for irradiating the observation range with the first excitation light;
(C) Second excitation light irradiation means for irradiating the sentinel lymph node with second excitation light,
(D) and the visible light obtained by irradiating the illumination light, the obtained by irradiating the first excitation light, the first fluorescence emitted from the cell Nchinerurinpa node detecting fluorescent substance, said second excitation light Imaging means for receiving and imaging the second fluorescence emitted from the fluorescent substance for detecting cancer cells / cancer tissue obtained by irradiating
(E) The first fluorescence emitted from the observation range obtained by irradiating the first excitation light and the cancer cell / cancer tissue detection fluorescent substance obtained by irradiating the second excitation light. Fluorescence measuring means for receiving the second fluorescence and measuring the fluorescence. Using two laparoscopic, there is provided an inspection apparatus for providing information for determining the metastasis of cancer cells or cancer tissue into sentinel lymph node within the observation range,
Of the laparoscopes, the first laparoscope comprises the following illumination light irradiation means (A) and the following image imaging means (D),
Of the laparoscopes, a second laparoscope includes the following first excitation light irradiation means (B), the following second excitation light irradiation means (C), and the following first and second fluorescence measurement purposes. An inspection apparatus using a laparoscope, comprising means (E) .
(A) Illumination light irradiation means for irradiating the observation range with illumination light;
(B) a first excitation light irradiation means for irradiating the observation range with the first excitation light;
(C) Second excitation light irradiation means for irradiating the sentinel lymph node with second excitation light,
(D) and the visible light obtained by irradiating the illumination light, the obtained by irradiating the first excitation light, the first fluorescence emitted from the cell Nchinerurinpa node detecting fluorescent substance, said second excitation light Imaging means for receiving and imaging the second fluorescence emitted from the fluorescent substance for detecting cancer cells / cancer tissue obtained by irradiating
(E) The first fluorescence emitted from the observation range obtained by irradiating the first excitation light and the cancer cell / cancer tissue detection fluorescent substance obtained by irradiating the second excitation light. Fluorescence measuring means for receiving the second fluorescence and measuring the fluorescence. An inspection device that uses three laparoscopes to provide information for determining metastasis of cancer cells / cancerous tissue to sentinel lymph nodes within the observation range,
Of the laparoscopes, a first laparoscope comprises the following illumination light irradiation means (A) and the following first excitation light irradiation means (B),
A second laparoscope of the laparoscopes includes the following image capturing means (D),
A third laparoscope of the laparoscopes comprises the following second excitation light irradiation means (C) and the following first and second fluorescence measurement means (E). Inspection device using a mirror.
(A) Illumination light irradiation means for irradiating the observation range with illumination light;
(B) a first excitation light irradiation means for irradiating the observation range with the first excitation light;
(C) Second excitation light irradiation means for irradiating the sentinel lymph node with second excitation light,
(D) Visible light obtained by irradiating the illumination light, first fluorescence emitted from the fluorescent material for sentinel lymph node detection obtained by irradiating the first excitation light, and the second excitation light. Imaging means for receiving and imaging the second fluorescence emitted from the fluorescent substance for detecting cancer cells / cancer tissue obtained by irradiating
(E) The first fluorescence emitted from the observation range obtained by irradiating the first excitation light and the cancer cell / cancer tissue detection fluorescent substance obtained by irradiating the second excitation light. Fluorescence measuring means for receiving the second fluorescence and measuring the fluorescence. An illumination light source for irradiating the illumination light;
A first excitation light source for irradiating the first excitation light;
A second excitation light source for irradiating the second excitation light;
A visible light imaging device for imaging the visible light;
A fluorescence imaging device for imaging the first fluorescence or the second fluorescence;
An image processing device for processing image information obtained by the visible light imaging device and the fluorescence imaging device;
A fluorescence spectrum measuring device for measuring a fluorescence spectrum from the first and second fluorescence;
A control device for controlling each light source and device;
A display device for displaying an output result from the device;
The inspection apparatus according to any one of claims 1 to 3, further comprising:

Images