JPH0414973B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION "Field of Industrial Application" The present invention relates to a cancer diagnostic device using light. Cancer treatment methods using photochemical reactions using fluorescent substances, such as hematoporphyrin derivatives (hereinafter referred to as HpD), which tend to accumulate in cancer and have a cell-killing effect when excited by light, are becoming established. teeth
It is called Photodynamic Therapy (PDT). The present invention relates to a diagnostic device that diagnoses cancer by measuring the spectral intensity and the like of fluorescence generated from this fluorescent substance.

"Conventional technology" In the diagnosis and treatment of cancer, a fluorescent substance with a strong affinity for cancer, such as HpD, is absorbed into the lesion area in advance, and this area is irradiated with laser light. A cancer diagnosis and treatment method and device for selectively necrotizing only cancer cells using a photochemical reaction with cancer have been proposed (Japanese Patent Publication No. 63-9464 and Japanese Patent Publication No. 63-2633).

FIG. 5 is a diagram showing the basic configuration of the conventional diagnostic treatment device proposed above, in which 1 indicates the tissue surface;
2, 3, 4, 5 are light guides, 6 is a color camera, 7 is a white light source, 8 is a laser light source, 9 is a spectrometer, 10 is a fluorescence spectrum image, 11 is a high-sensitivity camera, 12 is an analysis circuit, 13 and 14 is the monitor
TV, 15 is a fiber bundle, and 16 is a video signal.

The apparatus shown in FIG. 5 can be divided into a normal endoscopic diagnosis system 17 and a photochemical reaction diagnosis treatment system 18. The fiber bundle 15 is incorporated into an endoscope, and is opposed to a site suspected of being a lesion in a patient who has previously been intravenously injected with HpD.

The endoscopic diagnosis system 17 includes a white light source 7 for irradiating the tissue surface 1, a light guide 3 that guides the white light, an image guide 2 that guides an image of the tissue surface 1 to a color camera 6, and a white light source 7 for irradiating the tissue surface 1. 1 image with a color camera 6 and a monitor TV 13 on which the image obtained is displayed.

The photochemical reaction diagnosis and treatment system 18 is provided with a laser light source 8 that outputs pulsed laser light by switching between diagnostic light for diagnosis (wavelength: 405 nm) and therapeutic light for treatment (630 nm). These lights are guided to the affected area by the light guide 4 and irradiated thereon. Fluorescence generated by irradiation with diagnostic laser light during diagnosis is guided to a spectroscope 9 by a light guide 5. A fluorescence spectrum image 10 obtained by this spectroscope 9 is photographed by a high-sensitivity camera 11, and this output video signal 16 is subjected to arithmetic processing in an analysis circuit 12 to be graphically displayed and displayed on a monitor TV 14 as a spectrum waveform. Spectral image 10 is HpD
Shows a bimodal system of 630nm and 690nm characteristic of fluorescence,
In order to observe this spectrum, the spectral wavelength range of the spectroscope 9 is set to 600 to 700 nm.

Since the endoscopic diagnosis and the photochemical reaction diagnosis treatment are performed in parallel, the white light source 7 and the laser light source 8 irradiate the tissue surface 1 in a time-sharing manner. The fluorescence spectrum analysis system from the spectrometer 9 to the monitor TV 14 also operates intermittently in synchronization with the laser beam irradiation.

This device allows the operator to monitor
The location of cancer can be detected while viewing the tissue image on the TV 13 and the fluorescence spectrum waveform on the monitor TV 14 at the same time, and any cancer discovered here can be immediately treated by simply switching the excitation light to the treatment mode. This treatment is performed by selectively causing necrosis of only the cancerous area through a photochemical reaction between HpD remaining in the cancerous area and therapeutic light. Furthermore, when confirming fluorescence at the time of diagnosis, since the spectral waveform unique to HpD itself is directly observed, there is no confusion with autofluorescence from normal areas, making it easier to identify cancer. In particular, it has the potential to greatly contribute to the diagnosis and treatment of early-stage cancer.

The wavelength of the treatment light was set to 630nm because, among the several absorption wavelengths of HpD, absorption by blood is the lowest at this wavelength, allowing the laser light to reach deep into the tissues and is expected to treat deep cancers. Because you can. Also, the wavelength of the diagnostic light was set to 405nm.
This is because the absorption of HpD is large at this wavelength, and the fluorescence unique to HpD can be efficiently generated.

``Problem to be Solved by the Invention'' The above-mentioned prior art is of great significance in itself because it allows diagnosis and treatment of cancer to be performed simultaneously with one device. Furthermore, the use of pulsed laser light with a large peak output as the light for exciting HpD is of great significance for effective diagnosis and treatment. However, there are cases where diagnosis and treatment are not performed at the same time, and there has been a particular desire for a device that can only perform diagnosis. For example, at the research level, there are cases where only a cancer diagnosis device is required, and there is a demand for a cancer diagnosis device that is particularly easy to use in health checkups for a large number of people.

If only diagnosis is to be performed, the conventional device described above can be used, but its dimensions are too large and it is difficult to move. Furthermore, if only for diagnosis, the 405 nm wavelength light source does not necessarily have to be a laser, but it is preferable to use a light source that is easy to use.

In conventional equipment, 405nm pulsed laser light for diagnosis was obtained by irradiating excimer gas laser light that emits 308nm light onto a dye solution in which a dye that emits 405nm light was dissolved in a solvent. These gases and dye solutions must be replaced with fresh ones at appropriate times to maintain laser performance. Although it depends on the frequency of use, it generally needs to be replaced once a week.

The present invention has only diagnostic considerations in mind and aims to provide a device using a light source that is small, lightweight, portable, and does not use gases or dye solutions.

"Means for Solving the Problems" The cancer diagnostic device of the present invention uses 405 nm, which was used only to obtain fluorescence from the affected area in the conventional technology.
The use of a pulsed laser light source that emits light has been eliminated, and instead a white light source that was used only to illuminate the tissue surface to obtain observation light is used not only for this purpose but also as a light source that emits 405 nm diagnostic light. It is characterized by

Therefore, the present invention uses a substance that has an affinity for cancer cells and emits fluorescence when excited by light, and irradiates the substance to be diagnosed, such as cells containing this substance or biological cells, with light. A device for diagnosing cancer using a white light source for obtaining fluorescence and observation light from a substance to be diagnosed, a light processing device for obtaining diagnostic light and observation light from the light of the white light source, and irradiation from the white light source. A light guide that guides light to the substance to be diagnosed and guides fluorescence and observation light, which are the optical information obtained from the light guide, to a spectrometer and an imaging camera, respectively, and a light guide for capturing an observation image using the observation light from this light guide. An imaging camera, a spectrometer for separating fluorescence using diagnostic light from a light guide, a camera for capturing a spectral image of fluorescence obtained from this spectrometer, and a computer that processes the video output of this camera. This device is characterized by comprising an analysis circuit for converting the spectrum into a spectral figure as a fluorescence spectral image, and a monitor TV for displaying the observed image and the fluorescence spectral image.

"Operation" Diagnostic light (for example, diagnostic light with a wavelength of 405 nm) and observation light (for example, white light) are obtained from a white light source by the light processing device. Then, the fluorescence obtained when the diagnostic light is irradiated is separated by a spectrometer, and the spectral image is captured by a camera (for example, a high-sensitivity camera).
The image is taken with This spectral image is converted into a figure through calculation analysis by an analysis circuit, and then displayed on the monitor TV.
is displayed. Furthermore, when the observation light is used, it is detected by an imaging camera (for example, a color camera), and the entire image of the observed substance is displayed on a monitor TV (for example, a monitor TV that is different from the monitor TV that displays the spectral image).

“Example” An example of the present invention will be described below with reference to the drawings.

FIG. 1 is a configuration diagram of the cancer diagnostic device of the present invention, and the fifth
The laser light source 8 and light guide 4 are removed from the conventional device shown in the figure, and the white light source 7 and light guide 3 are removed.
A light processing device 19 is interposed between the two. The roles of the other components are exactly the same as those in FIG.

As shown in FIGS. 2 and 3, the optical processing device 19 includes a motor 20, a tipper disk 21 rotated by the motor 20, and a chopper disk 21 rotated by the motor 20.
and a control circuit 22 that controls the timing of the high-sensitivity camera 11. The disc 21 for the chiyotsupa
Diagnostic light windows 24a to 24d are provided with filters 23 to obtain diagnostic light in the wavelength range of 400 to 410 nm with a center wavelength of 405 nm, and holes with nothing attached to obtain observation light of all wavelengths. Observation light windows 25a to 25d with open spaces are formed alternately.

White light generated from a white light source 7 such as a Xe lamp turned on by a power source 26 is focused by a lens 27, enters the light guide 3, and irradiates the tissue surface 1 of a living body as a substance to be diagnosed. do. At this time, the white light is chopped by a chopper disk 21 attached to a motor 20. The rotation of the motor 20 is controlled by a timing control circuit 22, and the rotation speed is set in a certain time relationship with the high-sensitivity camera 11 by the timing control circuit 22.

405nm for diagnosis during rotation of Chiyotupa disc 21
The respective temporal relationships of HpD fluorescence obtained by irradiation with light, observation white light, and 405 nm light are shown in FIG. As mentioned above, HpD fluorescence can be obtained by irradiation with 405 nm light. Disc 2 for chiyotsupa
1 is rotated at 15Hz (15 rotations per second), this will cause the 405nm diagnostic light to rotate at 60 pulses/
It becomes a pulse train of seconds (period is 1/60 seconds).
The pulse width of the 405nm diagnostic light is 2ms, and the pulse width of the observation white light is 10ms.
It starts rising after 2.7ms. Note that this time relationship is determined by the window size of the tipper disc 21 and the rotational speed of the motor 20.

Although HpD fluorescence can be obtained both by 405 nm light and by white light irradiation, the cancer diagnostic device of the present invention detects the HpD fluorescence obtained only by 405 nm light.
This is done by gate operation of the high-sensitivity camera 11. This high-sensitivity camera 11 consists of a combination of image intensifier (hereinafter referred to as II) SIT image pickup tubes, and a weak fluorescence spectrum image 10 formed on the incident photocathode of II is amplified on the fluorescent screen at the output end. The SIT image pickup tube is for capturing the output image of this II, and the output image is displayed on the monitor TV 14 through the analysis circuit 12. The gate operation of the high-sensitivity camera is performed by supplying and stopping the voltage applied to II necessary for amplification. It takes advantage of the fact that the amplification function occurs only when voltage is supplied. Specifically, in Figure 4, voltage is supplied to II and the gate is turned on only when 405 nm diagnostic light is incident on the light guide.
The high-sensitivity camera 11 is operated, and when irradiating white light,
The voltage supply to II is stopped, the gate is turned off, and the high-sensitivity camera 11 is rendered inoperable. The timing control circuit 22 is configured to turn on the gate II only when the 405 nm diagnostic light enters the light guide 3, and turn off the gate II when the white observation light enters the light guide 3. This is for timing the rotation of the plate 21 and the gate operation. The gate is closed when this white observation light is irradiated.
By turning it OFF, photodestruction of II due to strong white light is avoided.

As described above, diagnostic light is obtained from one white light source and a fluorescence spectral image is displayed on a monitor TV, while the overall image is also monitored using observation light.
Display on TV.

In the embodiment described above, two monitors were used: the monitor TV 13 that displays the image obtained by photographing the tissue surface 1 with the color camera 6, and the monitor TV 14 that displays the fluorescence spectroscopic image obtained from the tissue surface 1. You can get away with using a monitor TV. It is common practice to electrically process multiple images and display them on a single TV monitor.

In the embodiment described above, nothing is attached to the observation light windows 25a to 25d of the chipping disc 21, but a filter is installed here to cut only the 405 nm diagnostic light component of white light within a range that does not disturb the color balance. You can also add Specifically, a cut filter that transmits wavelengths longer than 410 nm is suitable. This allows HpD to be photolyzed by exposing it to too much light during diagnosis,
As a result, deterioration in diagnostic reproducibility is reduced.

In the embodiment described above, the white light source 7 used was a Xe lamp that emits light, so-called white light, which does not have any partial loss of spectral components and covers the spectrum of the entire visible region on average.

However, the light is not limited to this white light, and may be a so-called white laser. An example of this white laser is a He-Cd hollow cathode laser. This is 442nm (blue), 534,
It simultaneously generates emission line spectra of only the three primary colors of 538 nm (green) and 636 nm (red), and is called a white laser because when these spectra are mixed, it appears white. In the present invention, this type of white laser can also be used as the white light source 7. For example, when the above He-Cd hollow cathode laser is used as the white light source 7, the diagnostic light windows 24a, 24b, 24 of the chipper disc 21 are
The filters 23 attached to c and 24d may be filters that pass only 442 nm light. The absorption of HpD is
There is a peak at 405nm, but there is also absorption at 442nm, so this light is absorbed and produced at 630nm, which is unique to HpD.
It can generate bimodal fluorescence at 690nm. In addition, the white light passing through the observation light windows 25a, 25b, 25c, and 25d illuminates the tissue surface with white light, and the observation image is captured by the color camera 6 on the monitor TV1.
For those displayed in 3, white color is reproduced. Even if a white laser is used as a white light source in this way, the spirit of the present invention is still valid and is within the scope of the present invention.
"Effects of the Invention" Since the present invention has the above configuration, the following effects can be obtained.

(1) Cancer diagnosis can be performed using a simple method using only a white light source, without using a 405 nm pulsed laser and a white light source as in the past, and the device is easy to handle, requires no maintenance, and is more compact. Ru. The spectral image obtained on the monitor TV is
If it is unique to HpD, it means that the diagnosed lesion contains HpD.
Since HpD has a strong affinity for cancer, it can be assumed that the lesion is cancerous.

(2) The use of HpD as a fluorescent substance with affinity for cancer and a cell-killing effect when photoexcited is not limited, but the use of other fluorescent substances with similar properties, such as pheophobide, metasphthalocyanine, and chlorophyll. The present invention can also be applied to the following types. Simply attach a filter with a transmission wavelength that matches the absorption wavelength of each fluorescent substance to the window of the chipper disc, and set the spectrometer's spectral wavelength range so that it can detect the fluorescence wavelength emitted by each fluorescent substance. .

[Brief explanation of drawings]

Fig. 1 is a block diagram showing an embodiment of the cancer diagnostic device according to the present invention, Fig. 2 is a block diagram of the main parts of the same, Fig. 3 is a front view of the chopper disc, and Fig. 4 is the output waveform of each part. FIG. 5 is a block diagram showing the configuration of a conventional device. 1... Tissue surface, 2, 3, 4, 5... Light guide, 6... Color camera, 7... White light source, 8
... Laser light source, 9 ... Spectrometer, 10 ... Fluorescence spectrum image, 11 ... High sensitivity camera, 12 ... Analysis circuit, 13, 14 ... Monitor TV, 15 ... Fiber bundle, 16 ... Video signal , 17... Endoscopic diagnosis system, 18... Photochemical reaction diagnosis treatment system, 19...
...Light processing device, 20...Motor, 21...Chopper disc, 22...Timing control circuit, 23...
...Filter, 24a-24d...Diagnostic light window, 2
5a to 25d... Observation light window, 26... Power supply, 2
7...Lens.

Claims (1)

[Claims] 1. Using a substance that has affinity for cancer cells and has the property of emitting fluorescence when excited by light,
In an apparatus that diagnoses cancer by irradiating a substance to be diagnosed such as a cell or a living cell containing this substance with light, a white light source is provided to obtain fluorescence and observation light from the substance to be diagnosed, and a diagnosis is made from the light of the white light source. A light processing device for obtaining light and observation light, and guiding the irradiation light from the white light source to the substance to be diagnosed, and guiding the fluorescence and observation light, which are optical information obtained from this, to a spectrometer and an imaging camera, respectively. a light guide, the imaging camera for capturing an observation image using the observation light from the light guide, the spectrometer for separating fluorescence using the diagnostic light from the light guide, and the fluorescence obtained from the spectrometer. a camera for capturing a spectral image of the camera, an analysis circuit for computationally processing the video output of this camera and converting it into a spectral figure as a fluorescence spectral image, and a monitor TV for displaying the observed image and the fluorescence spectral image. A cancer diagnostic device comprising: 2. The optical processing device has a diagnostic light window with a filter attached to it that transmits only the diagnostic light, and an observation light window for obtaining observation light arranged alternately around the rotating shaft on a chipper disc. The cancer diagnostic device according to claim 1. 3. The cancer diagnostic apparatus according to claim 2, wherein the window for observation light of the chiyotsupa comprises only a hole with nothing attached thereto. 4. The cancer diagnostic apparatus according to claim 2, wherein the observation light window of the chip is provided with a filter that does not transmit wavelength components matching the diagnostic light among the white light emitted from the white light source. 5. The camera for capturing a fluorescence spectrum image is controlled to capture an image only when diagnostic light is irradiated from a white light source, and not to capture an image when observation light is irradiated. cancer diagnostic equipment. 6. A claim in which the substance that emits fluorescence is a hematoporphyrin derivative (HpD), the transmission wavelength of the filter attached to the diagnostic light window of the chiotsuba disc is 405 nm, and the white light source is a xenon lamp. 2. The cancer diagnostic device according to 2.