JP5030664B2 - Endoscope device - Google Patents

Description

  The present invention relates to an endoscope apparatus.

  It is known that there is a difference in the amount of molecules expressed, cell activity, etc. between abnormal tissues such as cancer and other normal tissues, and this difference is expressed by fluorescence intensity using a fluorescent probe (fluorescent dye). A method has been proposed in which an abnormal tissue is identified endoscopically by observing as a difference (see, for example, Patent Document 1).

JP-A-10-201707

Patent Document 1 discloses an endoscope for diagnosing by observing a difference between an abnormal tissue and a normal tissue (difference in the accumulation of fluorescent probes) using one type of fluorescent probe.
In the field of microscopic observation, an enzyme-sensitive fluorescent probe (for example, FDA; esterase-sensitive probe) used for cell viability discrimination is known. This fluorescent probe is a fluorescent probe that changes in fluorescence depending on the esterase present in the cytoplasm, and the speed at which it changes to a fluorescent molecule varies depending on the amount and activity of esterase. It is desired to effectively use this fluorescent probe for discrimination between abnormal tissue and normal tissue in endoscopic observation.

  However, since the enzyme activity depends on temperature, when an enzyme-sensitive fluorescent probe is used for endoscopic observation, when the surface of the living body to be observed is affected by temperature, the rate of change to a fluorescent molecule is increased. There is a problem that it is difficult to observe the difference in fluorescence intensity between normal and abnormal tissues due to being too fast or too slow.

  The present invention has been made in view of the above-described circumstances, and is an endoscope that can accurately diagnose whether a living tissue to be observed is a normal tissue or an abnormal tissue by fluorescence observation using an enzyme-sensitive fluorescent probe. The object is to provide a mirror device.

In order to achieve the above object, the present invention provides the following means.
The present invention relates to an insertion part that is inserted into a body cavity of a living body, a light source part that generates excitation light emitted from the distal end of the insertion part toward the inner wall of the body cavity, and a body cavity by excitation light emitted from the light source part An imaging unit that captures fluorescence generated from the inner wall, a liquid feeding unit that has a pipe that supplies liquid to be discharged from the tip of the insertion unit, and a liquid that controls the temperature of the liquid flowing in the pipe of the liquid feeding unit A temperature control unit , wherein the pipe line is formed by a channel penetrating in the insertion portion in the longitudinal direction, and the liquid temperature control unit is disposed around the channel in the vicinity of the distal end of the insertion unit. to provide an endoscope apparatus in which Ru with a heater.

In the above SL invention, the imaging unit is provided at the distal end of the insertion portion, the heater may be that provided at the base end side of the insertion portion from the imaging unit.

Moreover, in the reference example of the above invention, the insertion portion is provided with a channel penetrating in the longitudinal direction, and the conduit is formed by a tube that is removably inserted into the channel, and the liquid temperature control portion is the tube. It is good also as providing the heater arrange | positioned in.
Moreover, in the said invention, the said liquid feeding part is provided with the container which stores the said liquid, and the said liquid temperature control part is good also as providing the thermostat which maintains the liquid in the said container in a constant temperature state.

  Moreover, in the said invention, the said liquid temperature control part is good also as controlling the said liquid to the temperature substantially equivalent to the body temperature of the said biological body.

  According to the present invention, even when an enzyme-sensitive fluorescent probe is used for endoscopic observation, by performing fluorescence observation while maintaining the temperature environment at the time of observation, the biological tissue to be observed is a normal tissue. There is an effect that it is possible to accurately diagnose whether the tissue is abnormal.

  As shown in FIG. 1, an endoscope apparatus 1 according to the present embodiment includes an insertion unit 2 that is inserted into a body cavity of a living body, an imaging unit 3 that is disposed in the insertion unit 2, and excitation light. A light source unit 4 that emits light, a liquid feeding unit 20 that supplies liquid to be discharged from the distal end 2a of the insertion portion 2, a control unit 5 that controls the imaging unit 3, the light source unit 4, and the liquid feeding unit 20, and the imaging unit. 3 and a display unit 6 for displaying the image acquired by 3.

  The insertion portion 2 has an extremely thin outer dimension that can be inserted into a body cavity of a living body, and a light guide 7 that propagates light from the light source unit 4 to the tip 2a therein, a channel that penetrates in the longitudinal direction. 23, a heater 26 for heating the liquid flowing in the channel 23, and the imaging unit 3.

  The light source unit 4 illuminates a subject to be imaged in the body cavity and emits illumination light for obtaining a white image, and a fluorescent material that is irradiated to the subject to be imaged in the body cavity and exists in the subject to be imaged Are provided with a special observation light source 9 that emits excitation light for generating fluorescence and a light source control circuit 10 that controls these light sources 8 and 9.

  The white observation light source 8 is, for example, a combination of a xenon lamp and a bandpass filter (not shown), and the 50% transmission regions of the bandpass filter are 420 to 470 nm, 500 to 580 nm, and 570 to 650 nm. That is, the white observation light source 8 can emit blue illumination light having a wavelength band of 420 to 470 nm, green illumination light having a wavelength band of 500 to 580 nm, and red illumination light having a wavelength band of 570 to 650 nm.

The special observation light source 9 is, for example, a semiconductor laser that emits excitation light having a peak wavelength of 490 ± 5 nm (or an argon laser that emits excitation light of 488 ± 5 nm). This semiconductor laser can excite a fluorescent probe having a fluorescein skeleton.
The light source control circuit 10 operates the white observation light source 8 and the special observation light source 9 at a predetermined timing.

As the fluorescent probe, an enzyme-sensitive fluorescent probe whose fluorescent property changes depending on the enzyme, for example, an esterase-sensitive fluorescent probe (FDAcr) having a fluorescein skeleton is used. The esterase-sensitive fluorescent probe does not emit fluorescence before the reaction with esterase. However, it has the property of being changed to a fluorescent substance having a light absorption peak near 490 nm and a peak near 510 nm by esterase which is a hydrolase present in the cytoplasm.
Since the abundance of esterase is higher in abnormal tissues such as cancer than in normal tissues, the rate of change to fluorescein is faster in abnormal tissues. Therefore, stronger fluorescence can be obtained from an abnormal tissue than a normal tissue by irradiating excitation light from a semiconductor laser.
A fluorescent probe solution in which the fluorescent probe is dissolved is stored in a tank 21 described later.

  The imaging unit 3 includes, for example, an imaging optical system 11 that collects light incident from the imaging target, an excitation light cut filter 12 that blocks excitation light incident from the imaging target A, and an operation of the control unit 5. The variable spectroscopic element 13 whose spectral characteristics can be changed by the above, and the image sensor 14 that captures the light collected by the image pickup optical system 11 and converts it into an electric signal.

The variable spectroscopic element 13 includes, for example, two plate-like optical members 13a and 13b that are arranged at a parallel interval and provided with a reflection film on the opposing surface, and an actuator that changes the interval between the optical members 13a and 13b. It is an etalon type optical filter provided with 13c. The actuator 13c is, for example, a piezoelectric element. The variable spectroscopic element 13 can change the wavelength band of the transmitted light by changing the distance between the optical members 13a and 13b by the operation of the actuator 13c.
More specifically, the variable spectroscopic element 13 has a transmittance wavelength characteristic having two transmission bands of one fixed transmission band and one variable transmission band. The fixed transmission band always transmits incident light regardless of the state of the variable spectroscopic element 13. Further, the transmittance characteristic of the variable transmission band changes according to the state of the variable spectroscopic element 13.

As shown in FIG. 1, the control unit 5 includes an image sensor control circuit 15 for driving and controlling the image sensor 14, a variable spectroscopic element control circuit 16 for driving and controlling the variable spectroscopic element 13, and a valve control circuit 25 described later. And an image storage unit 17 that stores image information acquired by the image sensor 14, and an image processing circuit 18 that processes the image information stored in the image storage unit 17 and outputs the processed image information to the display unit 6. .
The imaging element control circuit 15 and the variable spectral element control circuit 16 are connected to the light source control circuit 10, and are synchronized with the switching of the white observation light source 8 and the special observation light source 9 by the light source control circuit 10. The image pickup device 14 is driven and controlled.

  Specifically, when excitation light is emitted from the special observation light source 9 by the operation of the light source control circuit 10, the variable spectroscopic element control circuit 16 sets the state of the variable spectroscopic element as the first state and sets the imaging element control circuit. The image information 15 is output from the image sensor to the first frame memory 17A. When the illumination light is emitted from the white light source 8 by the operation of the light source control circuit 10, the variable spectral element control circuit 16 sets the variable spectral element to the second state, and the imaging element control circuit 15 starts from the imaging element. The output image information is output to the second frame memory 17B.

  In the case of fluorescence observation, the image processing circuit 18 receives fluorescence image information obtained by irradiation of excitation light from the first frame memory 17A and outputs it to the display unit 6, and in the case of white observation, Reflected light image information obtained by irradiation of blue, green, and red illumination light is received from the second frame memory 17B and output to the display unit 6.

  The liquid feeding unit 20 includes a tank 21 for storing the fluorescent probe solution, a tank 24 for storing the cleaning liquid, a thermostat 27 for maintaining the liquid in the tanks 21, 24 at a constant temperature, and the temperature of the thermostat 27. A temperature display unit 28 for displaying, a valve 22 for supplying / stopping liquid from the tanks 21, 24, and a channel 23 connected to the valve 22 for supplying liquid to the tip 2 a along the insertion unit 2. And a heater 26 for heating the liquid flowing in the channel 23, and a valve control circuit 25 disposed in the control unit 5 for controlling the valve 22.

The channel 23 is provided so as to penetrate the insertion portion 2 in the longitudinal direction, and the tip thereof is disposed at the tip 2a of the insertion portion 2 so that a liquid such as a sent fluorescent probe solution or a cleaning solution is directed toward an imaging target. Can be sprayed.
The heater 26 is disposed around the channel 23 in the vicinity of the distal end 2 a of the insertion portion 2 on the proximal end side from the imaging unit 3.

As shown in FIG. 3, the bulb control circuit 25 is configured to remove the fluorescent probe solution stored in the tank 21 for a predetermined time during the white light observation before the activation of the special observation light source 9 for obtaining a fluorescent image. The valve 22 is controlled to spray.
In addition, the valve control circuit 25 is configured to switch the valve 22 to the OFF state after the fluorescent probe solution is sprayed.

In addition, the valve control circuit 25 sprays a cleaning solution in order to clean the surface of the living body or to clean the fluorescent probe accumulated on the surface of the living body before and after the fluorescent probe solution is sprayed. The valve 22 is controlled. Further, the valve control circuit 25 is configured to switch the valve 22 to an off state after spraying the cleaning liquid.
For example, a low concentration acetic acid solution is used as the cleaning liquid.

The operation of the endoscope apparatus 1 according to the present embodiment configured as described above will be described.
In order to image the imaging target A in the body cavity of the living body using the endoscope apparatus 1 according to the present embodiment, first, the insertion portion 2 is inserted into the body cavity, and the distal end 2a thereof is the imaging target A in the body cavity. To face.

In this state, the light source unit 4 and the control unit 5 are operated, and the light source control circuit 10 is operated to operate the white observation light source 8 to generate illumination light, thereby performing white observation.
At this time, the generated illumination light is propagated through the light guide 7 to the distal end 2a of the insertion portion 2 and irradiated from the distal end 2a of the insertion portion 2 toward the imaging target A. The irradiated illumination light is reflected on the surface of the imaging target A, is collected by the imaging optical system 11, passes through the excitation light cut filter 12, and enters the variable spectral element 13.

Since the variable spectroscopic element 13 is switched to the second state by the operation of the variable spectroscopic element control circuit 16, all incident reflected light is transmitted through the variable spectroscopic element 13. The reflected light that has passed through the variable spectroscopic element 13 is incident on the image sensor 14 and the reflected light image information is acquired. The acquired reflected light image information is stored in the second frame memory 17B, and is output and displayed on the display unit 6 by the image processing circuit 18.

Thereafter, when observation using a fluorescent probe is performed, the valve 22 is connected to the channel 23 and the tank 24 for storing the cleaning liquid by the operation of the valve control circuit 25, and the cleaning liquid is sprayed on the living body and exists on the living body surface. Residue etc. to be washed away.
After spraying the cleaning liquid, the valve control circuit 25 operates to connect the channel 22 and the tank 21 storing the fluorescent probe solution, so that the fluorescent probe solution is sprayed on the living body.

  After the fluorescent probe solution is sprayed, the valve 22 connects the channel 23 and the tank 24 again by the operation of the valve control circuit 25, the cleaning liquid is sprayed, and the fluorescent probe solution present on the living body surface is cleaned. A certain period of time may be provided between the spraying of the fluorescent probe and the cleaning.

After cleaning, the light source control circuit 10 is operated to switch from the white observation light source 8 to the special observation light source 9, and the special observation light source 9 is operated to generate excitation light to perform fluorescence observation.
At this time, the generated excitation light is propagated through the light guide 7 to the distal end 2a of the insertion portion 2 and irradiated from the distal end 2a of the insertion portion 2 toward the imaging target A. As a result, the fluorescent probe penetrating the imaging target A is excited and emits fluorescence. The fluorescence emitted from the imaging target A is collected by the imaging optical system 11 of the imaging unit 3, passes through the excitation light cut filter 12, and enters the variable spectral element 13.

  Since the variable spectroscopic element 13 is switched to the first state by the variable spectroscopic element control circuit 16 and the transmittance for fluorescence is increased, the incident fluorescence is transmitted through the variable spectroscopic element 13. The fluorescence transmitted through the variable spectroscopic element 13 is incident on the image sensor 14 and fluorescence image information is acquired. The acquired fluorescence image information is stored in the first frame memory 17A, and is output from the display unit 6 and displayed by the image processing circuit 18.

  In this case, according to the endoscope apparatus 1 according to the present embodiment, the fluorescent probe solution and the cleaning liquid that are set to a predetermined temperature in advance by the thermostatic chamber 27 are supplied to the channel 23. Then, the fluorescent probe solution and the cleaning liquid flowing in the channel 23 are dispersed on the living body surface as the observation target A while being adjusted to a predetermined temperature by the heater 26. That is, by controlling the temperatures of the fluorescent probe solution and the cleaning solution, the temperature of the living body that is the observation target A is maintained at a temperature suitable for observation.

  Here, in cancer diagnosis using an enzyme-sensitive fluorescent probe, a normal tissue or an abnormal tissue such as cancer is observed by observing the difference in the fluorescent strength using the difference in the increase speed of the fluorescent strength of normal / abnormal tissue. As shown in FIG. 4, since the difference in fluorescence intensity between normal / abnormal tissues becomes smaller after a certain period of time, as shown in FIG. It is necessary to measure in the normal / abnormal tissue when the fluorescence contrast is the highest. However, since the reaction rate (activity of the enzyme) between the target molecule (enzyme) and the fluorescent probe is affected by temperature, it may be difficult to capture a time zone suitable for observation. Therefore, in order to obtain a fluorescence contrast suitable for diagnosis, it is desirable to control the reaction rate (enzyme activity) of the fluorescent probe by performing fluorescence observation under a predetermined temperature condition.

  According to the endoscope apparatus 1 according to the present embodiment, the reaction rate (activity of the enzyme) between the target molecule (enzyme) and the fluorescent probe is not affected by the temperature decrease of the tissue. As shown in FIG. 5, the fluorescence contrast is clear in normal / abnormal tissues, and a long time zone suitable for fluorescence observation in which a difference in fluorescence intensity appears greatly can be secured to accurately capture the fluorescence. Thereby, in cancer diagnosis using a spray-type enzyme-sensitive fluorescent probe, it is possible to accurately diagnose whether the biological tissue of the observation target A is a normal tissue or an abnormal tissue.

  If the room temperature is low, the temperature of the fluorescent probe solution and the cleaning solution stored in the tanks 21 and 24 decreases when flowing from the thermostatic chamber to the channel 23, so that the surface of the living body, which is the observation target A, remains as it is. When sprayed, the temperature of the living body surface will decrease. As a result, it is conceivable that the reaction rate between the target molecule (enzyme) and the fluorescent probe is slow (the enzyme activity is low). In this case, as in Comparative Example 1 shown in FIG. 5, since the increase rate of the fluorescence intensity is slow and the amount of fluorescence is weak, in order to obtain the fluorescence intensity necessary for observation, a long time was waited after administration of the fluorescent probe. In addition, since the fluorescent probe itself leaks from the cells little by little, the difference in fluorescence intensity is small even after waiting for a long time, making it difficult to distinguish between normal and abnormal tissues.

  On the other hand, according to the present embodiment, the temperature of the fluorescent probe solution and the cleaning solution is preliminarily warmed to a temperature substantially equal to the body temperature of the living body (approximately 37 ° C.) by the thermostatic chamber 27, and 37 again in the channel 23 by the heater 26. By heating around the living body surface, which is the observation target A, after heating to around 0 ° C., a temperature drop on the living body surface can be prevented. In other words, by using a fluorescent probe solution and a washing solution heated to around 37 ° C. where the activity of the enzyme increases, the reaction rate (activity of the enzyme) between the target molecule (enzyme) and the fluorescent probe is suitable for observation. Can be controlled to speed. Therefore, cancer diagnosis can be performed with high accuracy by performing observation in a time zone where fluorescence contrast is present in normal / abnormal tissues and a difference in fluorescence intensity is large.

Further, according to the present embodiment, the heater 26 is provided around the channel 23 even in an endoscope having a long length from the operation unit to the distal end 2 a of the insertion unit 2. It can prevent that the temperature of a solution and a washing | cleaning liquid falls. Further, since the heater 26 is provided in the vicinity of the distal end 2a of the insertion portion 2, the temperatures of the fluorescent probe solution and the cleaning solution are kept heated until immediately before discharge, and temperature management can be performed with high accuracy.
And since the heater 26 is provided in the base end side from the imaging unit 3, there is no possibility that the imaging unit 3 will be heated. Even in a very narrow space such as the distal end 2 a of the insertion portion 2, the heater 26 can be provided on the base end side of the imaging unit 3.

  Moreover, according to this embodiment, since a low concentration acetic acid solution is used for the cleaning liquid, mucus can be removed from the living body surface that is the observation target A. That is, since this acetic acid decomposes the mucus component that hinders staining of living tissue, the fluorescent probe is easily fixed on the surface of the living body. Thereby, fluorescence observation can be performed with high accuracy.

  In the endoscope apparatus 1 according to the present embodiment, the heater 26 is provided around the channel 23. Instead of this, as shown in FIG. The tube 29 may be provided, and the heater 26 may be provided around the tube 29. The heater 26 may be provided on the tube 29 itself, or may be provided on a part of the inner surface of the tube 29. In this case, the fluorescent probe solution and the cleaning liquid may be poured into the tube 29 with a syringe or the like.

Further, the tip of the tube 29 may be configured to spray the liquid in a spray form. With such a configuration, there is an advantage that the fluorescent probe solution and the cleaning solution are more easily distributed on the surface of the living body as the observation target A than when the fluorescent probe solution and the washing solution are allowed to flow directly through the channel 23.
Moreover, in the endoscope apparatus 1 according to the present embodiment, the constant temperature bath 27 is provided together with the heater 26, but only the heater 26 may be provided and the constant temperature bath 27 may not be provided.

  On the contrary, as shown in FIG. 7, only the constant temperature bath 27 may be provided without providing the heater 26. In particular, a narrow internal view in which the space in the insertion portion 2 is narrow so that the heater 26 cannot be provided in the channel 23, and the heater 26 is not provided in the tube 29 inserted into the channel 23. In the case of the mirror device 1, there is an advantage that the same effect as described above can be obtained by providing the thermostatic chamber 27 outside the insertion portion 2. In this case, it is desirable that the channel 23 is made of a heat insulating material. By configuring in this way, it is possible to prevent the temperature of the fluorescent probe solution and the cleaning solution heated by the thermostatic chamber 27 from changing while flowing in the channel 23. At this time, the tube 29 may be warmed using a thermostatic bath or the like before use.

Here, when the reaction speed between the target molecule (enzyme) and the fluorescent probe is fast (the enzyme activity is high), the fluorescence intensity is detected in normal / abnormal tissues as in Comparative Example 2 shown in FIG. The time period in which the difference occurs is short and it is necessary to observe immediately after administration of the fluorescent probe, making it difficult to distinguish between normal and abnormal tissues.
On the other hand, according to the present embodiment, the temperature of the living body surface is lowered by spraying the cleaning solution and the fluorescent probe solution cooled in advance in the thermostat 27 on the living body surface to be observed, and the target molecule (enzyme) ) And the fluorescent probe can be slowed down (enzyme activity is lowered), and the time zone in which the difference in fluorescence intensity appears can be extended. Thereby, observation time is ensured and cancer diagnosis can be performed accurately.

  Specifically, for example, when fluorescein diacetate (FDA) is used as a fluorescent probe, the reaction rate with a target molecule (enzyme) is too high at a temperature approximately equal to the body temperature of a living body (approximately 37 ° C.). It is conceivable to perform fluorescence observation by slowing the reaction rate by spraying the fluorescent probe solution and the washing liquid cooled to about 15 ° C. in the tank 27 on the surface of the living body to be observed and lowering the temperature of the living body surface. .

In the present embodiment, one channel 23, valve 22 and constant temperature bath 27 are arranged for the tank 21 for storing the fluorescent probe solution and the tank 24 for storing the cleaning liquid. The constant temperature bath 27 may be arranged for each of the tanks 21 and 24.
In the present embodiment, both the fluorescent probe solution and the cleaning solution are heated by the heater 26 and the constant temperature bath 27. However, only one of them is heated or cooled by the heater 26 or the constant temperature bath 27. May be.

1 is an overall configuration diagram of an endoscope apparatus according to an embodiment of the present invention. It is a figure which shows the structure of the imaging unit with which the endoscope apparatus of FIG. 1 is equipped. It is a timing chart which shows an example of observation operation by the endoscope apparatus of FIG. It is a graph which shows the time change of the fluorescence intensity by the endoscope apparatus of FIG. It is a graph which shows the comparative example 1 of the time change of the fluorescence intensity of FIG. It is a whole block diagram which shows the modification of the endoscope apparatus of FIG. It is a schematic block diagram which shows the other modification of the endoscope apparatus of FIG. It is a graph which shows the comparative example 2 of the time change of the fluorescence intensity of FIG.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Endoscope apparatus 2 Insertion part 2a Tip 3 Imaging unit (imaging part)
4 Light source unit (light source part)
6 Display unit 7 Light guide 8 Light source for white observation 9 Light source for special observation 20 Liquid feeding unit (liquid feeding part)
21, 24 Tank (container)
23 channels (pipe)
26 Heater (Liquid temperature controller)
27 Thermostatic chamber (liquid temperature controller)
29 tubes

Claims (4)

An insertion part to be inserted into a body cavity of a living body;
A light source unit that generates excitation light irradiated from the distal end of the insertion unit toward the inner wall of the body cavity;
An imaging unit that captures fluorescence generated from the inner wall of the body cavity by the excitation light emitted from the light source unit;
A liquid feeding section having a conduit for supplying a liquid to be discharged from the tip of the insertion section;
A liquid temperature control unit for controlling the temperature of the liquid flowing in the pipe line of the liquid feeding unit ,
The pipe line is composed of a channel provided through the insertion portion in the longitudinal direction,
The liquid temperature control unit, an endoscope apparatus Ru comprising a heater disposed around the channel in the vicinity of the distal end of the insertion portion. The imaging unit is provided at the distal end of the insertion unit,
The endoscope apparatus according to claim 1 , wherein the heater is provided on a proximal end side of the insertion portion with respect to the imaging portion. The liquid feeding part includes a container for storing the liquid,
The endoscope apparatus according to claim 1, wherein the liquid temperature control unit includes a thermostatic bath that maintains the liquid in the container in a constant temperature state. The endoscope apparatus according to any one of claims 1 to 3 , wherein the liquid temperature control unit controls the liquid to a temperature substantially equal to a body temperature of the living body.

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