JPH07155286A - Fluorescence observing apparatus - Google Patents

Abstract

PURPOSE:To make an apparatus miniaturized and inexpensive by providing the apparatus with a wave length controlling means which changes the wave length of a laser light by controlling the temp. of a semiconductor and changing selectively the range of wave length entered into a fluorescence detecting apparatus detecting fluorescence in accordance with change in wave length by using a filter means. CONSTITUTION:An electronic cooling and heating means 24 fitted on a laser diode 21 in an apparatus 5 for a light source for excitation for observing fluorescence is driven by a electric source circuit 25 for a heating means and they are controlled by a controlling means 26. This controlling means 26 is connected with a wave length selection indicating means and it controls the temp. of a laser diode 21 through the electronic cooling and heating means 24 in such a way that the laser diode 21 is made emitted by an indicated wave length. In addition, a controlling means 26 indicates selection of the wave length of the excited light and when the wave length of the fluorescence emitted by the excited light with the wave length, it indicates selection of the wave length and a filter through which the wave length of the fluorescence is selectively transmitted is set on a light path of a fluorescence photographing system through a filter switching control means 9.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a fluorescence observation apparatus for controlling the temperature of a laser diode to variably set the wavelength of excitation light.

[0002]

2. Description of the Related Art In recent years, autofluorescence from a living body or injection of a drug into a living body, the fluorescence of the drug is detected as a two-dimensional image, and from the fluorescence image, disease states such as degeneration of living tissue and cancer (eg, , Type of disease and extent of infiltration).

When light is applied to living tissue, fluorescence having a wavelength longer than that of the excitation light is generated. Examples of fluorescent substances in the living body include NADH (nicotinamide adenine nucleotide), FMN (flavin mononucleotide), and pyridine nucleotide. Recently, such an interrelationship between an endogenous substance and a disease has become clear. In addition, HpD (hematoporphyrin), Photofri
n, ALA (δ-amino levulinica
Cid) has the property of accumulating in cancer, and by injecting this into a living body and observing the fluorescence of the substance, the diseased site can be diagnosed.

By the way, when performing the above-mentioned fluorescence observation, it is general to irradiate a target diagnostic region with a laser beam for excitation. In this case, the excitation laser light needs to have a wavelength suitable for the excitation depending on the diagnosis site.

[0005]

Therefore, a plurality of lasers, a dye laser capable of oscillating a plurality of wavelengths, an alexandrite laser, or the like is required as an excitation laser device, which makes the device large and expensive. There was a drawback.

The present invention has been made in view of the above points, and an object of the present invention is to provide a fluorescence observation apparatus which can be reduced in size and cost.

[0007]

In the present invention, in a fluorescence observation apparatus using a semiconductor laser as an excitation light source for fluorescence observation, a laser emitted from the semiconductor laser is controlled by controlling the temperature of the semiconductor laser. By providing wavelength control means for changing the wavelength of light and filter means for selectively changing the wavelength range incident on the fluorescence detection device for detecting fluorescence according to the wavelength change by the wavelength control means, The wavelength range that can be used in semiconductor lasers has been expanded, making it possible to achieve smaller size and lower cost than when using other laser generators.

[0008]

Embodiments of the present invention will be described below with reference to the drawings. FIG. 1 shows the configuration of the fluorescence observation apparatus according to the first embodiment of the present invention. The fluorescence observation apparatus 1 of the first embodiment shown in FIG. 1 includes an endoscope 2, a TV camera 3 that is detachably attached to the endoscope 2 and that is equipped with image pickup means for normal observation and fluorescence observation. The endoscope light source device 4 for supplying illumination light for normal observation to the endoscope 2, the excitation light source device 5 for generating excitation light for fluorescence observation, and the TV camera 3 are connected to each other. CCU 6 for image processing, endoscopic image monitor 7 for displaying an endoscopic image by the output signal of CCU 6, and TV camera 3
Is connected to the fluorescence diagnostic device 8 for signal processing for generating a fluorescence image and displaying the fluorescence image, and the excitation light source device 5, and a filter used in the fluorescence imaging system in the TV camera 3 in accordance with the excitation light. Filter switching control means 9 for switching,
It comprises an observation switching means 10 for instructing switching between normal observation and fluorescence observation.

The endoscope 2 has an elongated insertion portion 11, an operation portion 12 provided at the rear end of the insertion portion 11, an eyepiece portion 13 provided at the rear end of the operation portion 12, and Operation part 1
2 and a light guide cable 14 extending from the light guide cable 14, and a light guide 15 for transmitting illumination light and excitation light is inserted into the insertion portion 11 and the light guide cable 14.

The light guide 15 is branched into two at the light guide cable 14 portion, and one end of the light guide cable 14a is connected to the endoscope light source device 4. Then, the lamp power supply circuit 1 in the endoscope light source device 4
The white light of the lamp 17 which emits light from the power source 6 is supplied to the end surface of the light guide 15 via the condenser lens 18. In the case of normal observation, the shading plate 19 is held in a retracted state as shown in FIG.

The other branch of the light guide cable 14 becomes a laser guide cable 14b, the end of which is connected to the excitation light source device 5, and the laser light from the laser diode 21 in the excitation light source device 5 is emitted. It is condensed by the condenser lens 22 and is irradiated. The laser diode 21 is driven by the power source from the laser diode power source circuit 23.

Further, an electronic cooling / heating means 24 is attached to the laser diode 21 by bonding or the like, and the electronic cooling / heating means 24 is powered by a power supply circuit 25 for the electronic cooling / heating means. Driven. The laser diode power supply circuit 23 and the electronic cooling / heating means power supply circuit 25 are connected to the control means 26 and controlled by the control means 26.

The control means 26 is connected to a wavelength selection instructing means (not shown). When the wavelength selection instructing means is operated to instruct the selection of the wavelength of the pumping light, the control means 26 is operated by the laser diode 21 at the wavelength instructed. The temperature of the laser diode 21 is controlled via the electronic cooling / heating means 24 so as to emit light.

The control means 26 reads the corresponding target temperature using the wavelength information as an address signal from the relation information between the emission wavelength of the laser diode 21 and the temperature recorded in, for example, a ROM (not shown), while the actual laser diode 21 is read.
On the basis of the output of a temperature sensor (not shown) that detects the temperature, whether to heat or cool when setting the target temperature is first judged, and after that judgment, the electronic cooling / heating means 24 is cooled or heated. A laser diode 2 is used in a feedback control loop so that the temperature operation is performed and the target temperature is matched.
Control to set and maintain 1 at the target temperature is performed.

The control means 26 is also connected to the filter switching control means 9, and when the wavelength of the fluorescence emitted by the excitation light of the wavelength changes with the wavelength selection instruction of the excitation light of the wavelength selection instruction means. When a wavelength selection instruction is given, the filter switching control means 9 is used to set on the optical path of the fluorescence imaging system such that the wavelength of the fluorescence is selectively transmitted (by a motor 42 described later). The filter turret 38 is rotated, and the filter arranged on the optical path is set to selectively transmit the wavelength of the fluorescence).

Further, instead of the wavelength selection indicating means,
A control means 26 is provided by providing means for selecting or instructing the type of fluorescence observation and selecting the fluorescent agent from this means.
Reads the wavelength of the laser light that efficiently excites the excitation light of the fluorescence observation wavelength generally used for the fluorescent agent from the ROM or the like, and the corresponding target temperature from the read wavelength (by the ROM or the like) The temperature of the laser diode 21 is controlled so as to obtain the target temperature, and the filter switching means 9 is controlled so that a filter that selectively transmits the wavelength of fluorescence observation is arranged on the optical path of the fluorescence imaging system. You can

As described above, in the first embodiment, the wavelength of the pumping light can be variably set by providing the wavelength control mechanism for controlling the temperature of the wavelength of the laser light emitted from the laser diode 21 as the pumping light. At the same time, the filter of the filter means for fluorescence observation on the side of the image pickup means can be selectively variably set according to the wavelength set as the excitation light.

The illumination light or excitation light transmitted through the light guide cable 14 and the light guide 15 in the insertion portion 11 is emitted from the end face of the insertion portion 11 on the distal end side, and illuminates a diagnosis site or the like. Reflected light or excitation light from the diagnostic region side forms an image on the front end surface of the image guide 32 arranged on the focal plane of the objective lens 31 attached to the observation window at the front end.

Then, it is transmitted to the end face on the eyepiece 13 side by the image guide 32, and in the case of white illumination light, it can be observed with the naked eye through the eyepiece lens 33. This eyepiece 13
When the TV camera 3 is attached to the
4. The image transmitted by the image guide 32 via the mirror 35 on the optical path is formed on, for example, the CCD 36 as an image pickup device.

The image pickup device is not limited to the CCD, but may be SIT (static induction transistor), CM.
D (Charge Modulation Device)
e), a MOS type image sensor or the like may be used.

When the mirror 35 is retracted from the optical path by the plunger 37, for example, as shown by the dotted line, the imaging lens 34, the filter of the filter turret 38 arranged on the optical path of the imaging lens 34, and the weak CCD 41 via an image intensifier 39 that amplifies light
Is imaged. The optical path shown by the dotted line in FIG. 1 becomes the optical path of the fluorescence imaging system, while the imaging lens 34, the mirror 35, and the CCD 36 arranged on the optical path shown by the solid line form the imaging system for normal observation.

The filter turret 38 is provided with a plurality of filters each having a different transmission region in the circumferential direction of the disc, and a motor 42 as a filter turret driving means drives one filter arranged on the optical path. Can be set selectively.

The mirror 35 in the TV camera 3 and the light blocking plate 19 in the endoscope light source device 4 are driven in conjunction with each other by operating the observation switching means 10. That is, when the normal observation switch in the observation switching means 10 is operated, the mirror 35 and the light shielding plate 19 are set to the state shown by the solid line in FIG. 1, and the subject image in the state illuminated by the white illumination light is formed on the CCD 36. The normal endoscopic image photoelectrically converted by the CCD 36 is signal-processed by the CCU 6, converted into a video signal that can be displayed on a monitor, and displayed on the endoscopic image monitor 7. That is,
A normal endoscopic image can be observed on the endoscopic image monitor 7.

On the other hand, when the fluorescence observation switch in the observation switching means 10 is operated, the mirror 35 and the light shielding plate 19 are moved to the positions shown in FIG.
The image of the fluorescent light in the state shown by the dotted line in FIG. 1 is illuminated by the excitation light, and the CCD image is transmitted through the filter of the filter turret 38 and the image intensifier 39.
The fluorescent image which is formed on 41 and photoelectrically converted by the CCD 41 is processed by a signal processing circuit in the fluorescent diagnostic device 8,
It is displayed on the monitor in the fluorescence diagnostic device 8.

According to the first embodiment, the temperature of the laser diode 21 is controlled so that the wavelength of the emitted laser light can be variably set. Therefore, one laser diode 21 can cover a wide wavelength range. Can be covered.

In this case, the laser diode 21 can be made extremely small, the electronic cooling / heating means 24 can also be made small, and the heat capacity of the laser diode 21 can be made small. This means that the temperature can be set to an arbitrary temperature in a wide range, and the wavelength of emitted light can be changed in a wide range. Therefore, it is possible to realize a compact excitation light generating laser device having a wide range of application without requiring a large laser device such as a dye laser.

Further, the TV camera 3 having the function of the fluorescence imaging system is provided with a filter turret 38 having a plurality of filters attached thereto, and the filter switching selection means 9 is provided.
Since the filter disposed on the optical path can be selectively set via the optical path, it is possible to perform fluorescence observation by setting a filter on the optical path that selectively transmits the wavelength of the fluorescence actually emitted. Further, in this embodiment, normal observation and fluorescence observation can be performed by a simple switching operation.

In FIG. 1, the laser guide cable 14b for transmitting the laser light joins the light guide cable 14a on the way, but the guide cable for transmitting the laser light is separated from the light guide 15 for transmitting the illumination light. May be provided. Alternatively, the laser guide may be inserted through the channel of the endoscope.

FIG. 2 shows a fluorescence observation apparatus 51 according to the second embodiment of the present invention. In the second embodiment, a second harmonic generating device (second harmonic generator device) is provided in front of the laser diode 21 'in the pumping light source device 5'.
52 is arranged so as to output the second harmonic of the laser light of the laser diode 21 ', that is, the laser light having a wavelength half the wavelength thereof. This laser diode 21 'is a laser diode that emits laser light having a long wavelength in the infrared region, and the wavelength thereof is 1 /
The laser light set to 2 becomes the wavelength of the excitation light.

The laser diode 21 'is pulsed (for example, the pulse period P is 1 / several hundreds) by the laser diode drive circuit 54 which outputs a pulsed drive current in response to a control pulse from the timing controller 53.
It is designed to emit a blinking light in S).

Further, the fluorescent image is formed on the CCD 41 without passing through the image intensifier 39 in the TV camera 3 in the first embodiment. CCDs 36 and 41 in the TV camera 3 are drivers 55 and 56, respectively.
Driven by. In this case, the CCD 36 is driven, for example, with a read cycle of 1 frame being 1 / 30S, while C
The CD 41 is driven at twice the pulse period P, and the image pickup signal of the CCD 41 is output when the excitation light pulse is output and when it is not output. Furthermore, the fluorescence diagnostic device 57 in this embodiment includes a two-dimensional lock-in amplifier 58,
It is composed of a CCU 59 and a monitor 60.

The two-dimensional lock-in amplifier 57 is the CCD
A / D converter 61 for converting the output signal of 41 into digital data and the timing controller 53,
A multiplexer 63 that divides each image data into a first frame memory 62a and a second frame memory 62b for each frame according to whether the laser diode 52 is turned on or off (flashes), and a first frame memory 62a and a second frame memory 62b. A difference circuit 64 that obtains the difference between the image data and cancels the noise component, and an integration circuit 65 that amplifies the image data from which the noise component has been canceled by cumulatively integrating (correspondingly adding the same corresponding pixel portion). It consists of and.

In the two-dimensional lock-in amplifier 57, the difference circuit 64 performs difference processing on the image data picked up by the light and darkness of the laser diode 52, thereby significantly reducing the noise component unrelated to the lightness and darkness. In addition, the influence of 1 / f noise which becomes conspicuous at a low frequency can be reduced, and the integration processing by the integration circuit 65 can generate fluorescence image data having a very high S / N.

By the integration processing by the integration circuit 65, image data of 1 / 30S is obtained, and D / (not shown)
After being converted to an analog image signal by the A converter, CCU5
9 is input to the monitor 9, converted into a standard video signal by the CCU 59, and a fluorescent image is displayed on the monitor 60.

In addition, the temperature of the laser diode 21 'is controlled to be twice the wavelength of the actually desired excitation light, and the configuration of selecting and setting the filter of the image pickup system according to the wavelength of fluorescence observed is the first. This is the same as in the first embodiment.

According to the second embodiment, instead of the laser diode 21 which directly emits the wavelength of the pumping light, a low-cost laser diode 21 'which generates a laser beam of a long wavelength which is twice the wavelength is used. Therefore, it can be realized at a lower cost. Further, by using the two-dimensional lock-in amplifier 57, a fluorescence image with very good S / N can be obtained. FIG. 3 shows an endoscope apparatus 7 according to the third embodiment of the present invention.
1 is shown. In the second embodiment, the laser diode 21 'and the like are provided in the excitation light source device 5 outside the endoscope 2, but in this embodiment, the laser diode 21' and the like are provided in the endoscope 72 and the external laser diode is used. The power supply circuit 73 supplies necessary power.

As shown in FIG. 4, the light guide 15 and the image guide 32 are inserted into the insertion portion 74 of the endoscope 72 in the same manner as in the first embodiment, and the illumination lens 75 and the objective are provided at the tip end portion. The lenses 31 and 31 are arranged respectively. In the endoscope 72, a laser diode 21 'attached to the electronic cooling / heating means 24, an SHG 52, and an illumination lens 76 are further arranged at the tip of the insertion portion 74.

The laser diode 21 'and the electronic cooling / heating means 24 are connected to a signal line 77, and the signal line 77 is branched from the light guide cable 14.
The laser diode drive circuit 54 of the laser diode power supply circuit 73 and the electronic cooling / warming means power supply circuit 25 are connected to the laser diode power supply circuit 73. Other than that, the configuration is the same as that of the second embodiment, and the function and effect thereof are almost the same as those of the second embodiment.

The laser diode 2 is inserted in the endoscope 72.
1'and the SHG 52 are housed, and an external laser diode 21 'is connected to the laser diode 21' via a signal line.
Alternatively, the drive signal may be supplied from the laser diode 21 'so that the pumping light having a half wavelength of the laser diode 21' can be emitted. Also in this case, there are the following advantages.

For example, when excitation light of 442 nm is required, a He--Cd laser is usually used, but
It is large and expensive. When this pumping light is required, a laser diode that emits a laser beam having a wavelength of 882 nm can be obtained at a low cost, and thus the same function can be realized at a low cost when used in place of the He-Cd laser. Also, since the laser diode can be made very small,
It can also be housed in the tip of the endoscope.

FIG. 5 shows an endoscope apparatus 8 according to the fourth embodiment of the present invention.
1 is shown. In this embodiment, a rigid endoscope 82, an endoscope light source device 4 for supplying illumination light for normal observation to a light guide of the rigid endoscope 82, and an excitation light source for supplying excitation laser light. Device 5'and eyepiece 83 of rigid endoscope 82
Connected to the scope holder 84, a TV camera 85 provided at the base end of the scope holder 84, and a TV
It is composed of an endoscopic image & fluorescent image display device 86 for performing signal processing for the camera 85 and displaying an endoscopic image and a fluorescent image.

The light guide cable 14 is connected to the light guide mouthpiece of the grip portion 90 formed at the rear end of the insertion portion 89 of the rigid endoscope 82, and one of the light guide cables 14a branched in the middle is viewed internally. It is connected to the mirror light source device 4, and white illumination light is supplied from the light source device 4.

The branched laser guide cable 14b of the light guide cable 14 is connected to the excitation light source device 5 ', which supplies the excitation laser light. The white illumination light or the excitation laser light is transmitted by the light guide in the rigid endoscope 82 and emitted from the end face on the tip end side.

Fluorescence emitted by the light reflected by the illuminated diagnostic site or the excitation light is imaged through the objective lens at the tip, and transmitted rearward by an image guide such as a relay optical system. In the case of a visible image, the image can be observed from the eyepiece 83.

The scope holder 84 connected to the eyepiece 83 has, for example, an arm portion containing a rod lens and
4a and a rotatable joint 84b, and an eyepiece 83
The image transmitted to the TV camera 85 connected to the base end of the image is transmitted.

A mirror 35 retractable by a plunger 37 is arranged on the incident optical path of the TV camera 85, and the light reflected by the mirror 35 is a second mirror 92 and a third mirror.
Is reflected by the mirror 93 and is imaged on the CCD 96 via the fourth mirror 95 which can be retracted from the optical path by the plunger 94.

When the mirrors 35 and 95 are retracted, an image is formed on the CCD 96 through the image intensifier 39 and the filter of the filter turret 98 rotated by the motor 97.

The filter of the filter turret 98 may be arranged on the optical path of the fluorescence imaging system via the motor 97 by a switch operation or the like. In this embodiment, a common CCD 96 is used to obtain a normal endoscopic image and a fluorescent image. Others have substantially the same effects as the first embodiment.

In order to widen the wavelength range of the excitation light,
A plurality of laser diodes having different emission wavelengths may be used, and the laser diode to be used may be selected according to the actually required wavelength of the excitation light.

In this case, SHG may be used if necessary. Further, in order to increase the light emission output, a plurality of laser diodes that emit light with the same wavelength may be used. The above-described embodiments may be partially combined.

[0051]

As described above, according to the present invention, the temperature of the semiconductor laser used for excitation light can be controlled to change the wavelength of emitted light, and the fluorescence from the target tissue side can be imaged with fluorescence. Since the filter means for selectively guiding the system is provided, a compact and low-cost fluorescence observation apparatus can be realized.

[Brief description of drawings]

FIG. 1 is a configuration diagram showing a configuration of a fluorescence observation apparatus according to a first embodiment of the present invention.

FIG. 2 is a configuration diagram showing a configuration of a fluorescence observation apparatus according to a second embodiment of the present invention.

FIG. 3 is a configuration diagram showing a configuration of a fluorescence observation apparatus according to a third embodiment of the present invention.

FIG. 4 is an explanatory diagram showing a structure of an optical system of an endoscope used in a third embodiment.

FIG. 5 is a configuration diagram showing a configuration of a fluorescence observation apparatus according to a fourth embodiment of the present invention.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 ... Fluorescence observation device 2 ... Endoscope 3 ... TV camera 4 ... Endoscope light source device 5 ... Excitation light source device 6 ... CCU 7 ... Endoscopic image monitor 8 ... Fluorescence diagnostic device 9 ... Filter switching control means 10 ... Observation switching means 11 ... Insertion part 13 ... Eyepiece part 14 ... Light guide cable 14b ... Laser guide cable 15 ... Light guide 17 ... Lamp 19 ... Shade plate 21 ... Laser diode 23 ... Laser diode power supply circuit 24 ... Electronic cooling / heating Means 25 ... Power supply circuit for electronic cooling / heating means 26 ... Control means 35 ... Mirrors 36, 41 ... CCD 38 ... Filter turret 39 ... Image intensifier

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Masahiko Iida 2-43-2 Hatagaya, Shibuya-ku, Tokyo Olympus Optical Co., Ltd. (72) Inventor Katsuya Suzuki 2-43-2 Hatagaya, Shibuya-ku, Tokyo Inside Olympus Optical Co., Ltd. (72) Inventor Yasuhiro Ueda 2-43-2 Hatagaya, Shibuya-ku, Tokyo Inside Olympus Optical Co., Ltd.

Claims (1)

[Claims] 1. A fluorescence observation apparatus using a semiconductor laser as an excitation light source for fluorescence observation, comprising: wavelength control means for changing the wavelength of laser light emitted from the semiconductor laser by controlling the temperature of the semiconductor laser. And a filter means for selectively changing a wavelength range incident on a fluorescence detection device for detecting fluorescence according to a wavelength change by the wavelength control means.