CN109758114A - Mating plate microscope for corneal nerve imaging - Google Patents
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- CN109758114A CN109758114A CN201910051384.2A CN201910051384A CN109758114A CN 109758114 A CN109758114 A CN 109758114A CN 201910051384 A CN201910051384 A CN 201910051384A CN 109758114 A CN109758114 A CN 109758114A
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Abstract
For the mating plate microscope of corneal nerve imaging, belong to corneal nerve technical field of imaging.Mating plate microscope includes control device, illumination path, image acquisition optical path, and the illumination path injects light into eye cornea, is formed at eye cornea and horizontal dynamic mating plate at α angle；Picture signal and horizontal at angle β emit obtain optical path into image, and described image obtains optical path and picture signal is sent into control device imaging；Wherein, the angle between the angle α and the angle β is 90 degree, and the angle α is not equal to 90 degree.The present invention carries out the acquisition of corneal nerve image using dynamic mating plate illumination microscope, accelerates image taking speed, reduces shooting time, avoids illumination light direct beam eyeground and damages to eyes.
Description
Technical field
The present invention relates to corneal nerve imaging fields, specifically carry out corneal nerve imaging device using mating plate microscope,
It can be widely used for biomedical ophthalmology technical field of imaging.
Background technique
Cornea is the part of eyes foremost, before iris and pupil.It is the most intensive group to innervate
It knits, most of corneal nerves are sensory nerves, come from trifacial thalamus branch.The cornea average level diameter of adult human eye
About 11.5 millimeters, perpendicular diameter is 10.5 millimeters, and curvature is still quite stable in entire life.Optic nerve area (pupil anterior angle
Film), the reflective functions of most of cornea are provided, 4 millimeters of diameter, are located at before Central corneal, pupil, under the conditions of photopic vision,
Cornea be the branch of avascular preceding arteria ciliares be parked in they form provide periphery cornea arc corneal limbus.Therefore,
Surrounding cornea and central cornea are all very different in terms of physiology and pathology.Corneal lamellar matrix (500 millimeters thick) is angle
Film provides structural intergrity.Interstitial keratocyte secretes collagen and proteoglycan, this be finally transparent basic cornea and
Aquation.
Cornea has nerve endings abundant, is one of tissue most sensitive in body, for keeping the integrality of ocular
Play a significant role.Research has shown that have many diseases related with corneal nerve, such as keratitis, dry eyes are sought peace diabetes.Cornea
Be it is transparent, no blood vessel is also without lymphatic vessel, but nerve fibre rich in.It is wherein mostly parasympathetic cholinergic
Nerve also has the adrenergic nerve of sympathetic nerve.
After the tiny white nerve of nineteen thirty Sohlamm first discovery enters cornea from corneoscleral junction, corneal nerve
Research method experienced the development in more than 70 years.From classical method of neurohistology, develop to using light microscopic and electron microscopic
Mirror is studied, and from immunohistochemical method is used, is developed to and is studied recently using Laser Scanning Confocal Microscope.Copolymerization is burnt aobvious
Micro mirror is to carry out viviperception to corneal nerve, becomes the imaging mode of clinical and scientific research mainstream at present.Corneal confocal is micro-
Mirror (corneal confocal microscopy, CCM) has the advantages that high-resolution, fine definition using laser as light source.
By continuous laser spot scan, the clear image of available live cornea each layer tissue and cell becomes clinical from thin at present
One of the important research means of the horizontal further investigated disease pathology mechanism of born of the same parents.Currently used is the cornea of Heidelberg company production
Confocal microscope mainly uses 63x times of Zeiss, and NA is 0.95 hydroscope, and the diode laser of 630nm carries out spot scan.Its
The speed for obtaining image is that 8 frames are per second, so each patient is typically necessary cost and gets required image in 5-15 minutes.
Because Laser Scanning Confocal Microscope is illuminated using the method for spot scan, the speed for causing image to obtain is slower, to each
Take a long time to keep a shooting posture for patient, and because when shooting corneal nerve object lens and eyeball pass through it is ophthalmically acceptable
Rubber cement contact, it is extremely uncomfortable that prolonged shooting will lead to patient's eye, needs to solve so shortening shooting time and being one
The problem of.
Mating plate fluorescence microscope (light sheet fluorescence microscopy) was widely used in recent years
In transparence imaging of tissue.The liver of animal, kidney etc. are organized after transparency process, the speed being imaged using mating plate fluorescence microscope
Degree is significantly faster than that confocal fluorescent microscopic, and imaging depth is advantageously.Hong in 2017 et al. proposes aobvious using mating plate
Micro mirror shoots the diagnosis that trabecular network is used for glaucoma, and the Bezier gauss laser of 488nm is used to excite in the equipment as illumination
Then light obtains the fluorescence signal reflected, the Bezier gauss laser in text is obtained using 176 degree of apex angle axicon lens.
In this image acquisition equipment, illumination path enters from the left side of eyeball, and image obtains optical path and reflects from trabecular network acquisition
Image information, shooting of this equipment for the trabecular network for the dynamic eyeball in zoopery, being likely to be suited for being removed, but people
Class has a right and left eyes, and there is the bridge of the nose in centre as separating, so this device and being not suitable for.And this lighting device is
Using static mating plate, in shooting process, the eyeball that needs to be taken is moved to as cooperating, so that the information of different depth is obtained,
But required for be easy to causeing moving distance not meet the problem of shooting depth.
Summary of the invention
In view of the problems of the existing technology the present invention, proposes a kind of mating plate microscope for corneal nerve imaging,
It can accelerate image taking speed, reduce shooting time, reduction of patient ophthalmic uncomfortable.
The technical scheme is that:
The present invention is used for the mating plate microscope of corneal nerve imaging, including control device, illumination path, image obtain optical path, institute
It states illumination path and injects light into eye cornea, formed at eye cornea and horizontal dynamic mating plate at α angle；Picture signal and water
It puts down at angle β emit and obtains optical path into image, described image obtains optical path and picture signal is sent into control device imaging；Wherein, the angle α
Angle between the angle β is 90 degree, and the angle α is not equal to 90 degree.
Preferably, mating plate microscope of the present invention further includes laser light source, the first lens group, reflection microscope group, the second lens
Group, camera sensor；The laser light source transmitting light successively enters eye angle through first lens group, the reflection microscope group
Film forms illumination path；Picture signal successively focuses on the camera through the reflection microscope group, second lens group and senses
Device forms image and obtains optical path.
Preferably, first lens group includes cylindrical lenses；The reflection microscope group include polygon scarnning mirror instrument, thoroughly
Mirror, object lens；The laser light source transmitting light enters institute by the polygon scarnning mirror instrument reflected light after cylindrical lenses focusing
Lens are stated, horizontally enter into the object lens later, are most formed at eye cornea finally and the horizontal dynamic mating plate at 45 degree of angles；Image
Signal and horizontal project at 135 degree of angles return to object lens, successively pass through the lens, the polygon scarnning mirror instrument, by described polygon
Enter second lens group after the reflection of scarnning mirror instrument.
Preferably, the reflection microscope group includes two points of mirrors, object lens, reflecting mirrors；Described in the laser light source transmitting light warp
After first lens group, You Erfen mirror is reflected into object lens, then vertically injects reflecting mirror, horizontally enters into after being reflected by reflecting mirror
Eye cornea；Picture signal and horizontal project at an angle of 90 degrees return to object lens, enter second lens group by two points of mirrors.
Preferably, first lens group includes amplifying lens group, cylindrical lenses, uniaxial scanning galvanometer, lens group.
Preferably, first lens group includes amplifying lens group, twin shaft scanning galvanometer, lens group.
Preferably, the reflecting mirror and level are fixed on the object lens at 45 degree of angles.
Preferably, the laser light source is the laser light source for emitting near infrared light.
Preferably, the wavelength of the laser light source transmitting light is 400-1100nm.
Preferably, mating plate microscope of the present invention further includes axicon lens, it is set to the laser light source and first lens group
Between, the laser light source transmitting light forms Bezier light into first lens group after the axicon lens.
The invention has the following advantages:
The present invention is used for the mating plate microscope of corneal nerve imaging:
1, since cornea is hyaline tissue, the present invention carries out the acquisition of corneal nerve image using dynamic mating plate illumination microscope,
Due to its illumination light can't direct projection eyeground, injury of the illumination light to eyes can be reduced.Laser illuminator uses near-infrared simultaneously
Light not only increases imaging depth, but also reduces the uncomfortable degree of patient's eye.
2, due to the present invention using dynamic mating plate illumination replace current Laser Scanning Confocal Microscope in spot scan illuminate, accelerate at
As speed, shooting time is reduced.
3, the acquisition that different optical paths carries out corneal nerve image can be used according to different requirements,.
4, the present invention uses lens group structure, is easily integrated and has good adaptive capacity to environment, facilitate the small of equipment
Type and portability.
Detailed description of the invention
Fig. 1 is the positional diagram using light and eyes when existing Laser Scanning Confocal Microscope；
Fig. 2 be using the present invention under one embodiment of mating plate microscope (referring to Fig. 4) of corneal nerve imaging light with
The positional diagram of eyes；
Fig. 3 is using the present invention for the light under another embodiment of mating plate microscope (referring to Fig. 7) of corneal nerve imaging
With the positional diagram of eyes；
Fig. 4 is mating plate microscopical embodiment structure schematic diagram of the present invention for corneal nerve imaging；
Fig. 5 is a certain exemplary construction schematic diagram of the first lens group in Fig. 4；
Fig. 6 is that position view is arranged in reflecting mirror in Fig. 4；
Fig. 7 is mating plate microscopical another embodiment structure schematic diagram of the present invention for corneal nerve imaging；
Fig. 8 is a certain exemplary construction schematic diagram of the second lens group in Fig. 7；
Fig. 9 is the example signal that the present invention forms Bezier light for the microscopical laser light source of mating plate of corneal nerve imaging
Figure.
Specific embodiment
Following is a specific embodiment of the present invention in conjunction with the accompanying drawings, technical scheme of the present invention will be further described,
However, the present invention is not limited to these examples.
Fig. 1 show Laser Scanning Confocal Microscope in use, light and eyes positional diagram.Laser light source emits light
After 213 direct projection eyeballs 211, in 212 backtracking object lens of image information.That is, illumination path is by luminous injection eye angle
Film, emit light at eye cornea with horizontal at an angle of 90 degrees, picture signal transmitting light returns in object lens, picture signal and it is horizontal at
An angle of 90 degrees, i.e. illumination path obtain optical path with image and coincide at eye cornea.Under this mode, due to emitting light direct beam eye
Bottom, so that patient's eye generates discomfort.Also, the spot scan method of Laser Scanning Confocal Microscope is illuminated, and causes image taking speed slow,
More exacerbate eyes sense of discomfort.For this purpose, the invention proposes a kind of mating plate microscopes for corneal nerve imaging.
In general mating plate microscope is only applicable to transparence imaging of tissue, the transparency cornea of protrusion eyeball front end is transparent
, it is able to use the imaging that mating plate microscope carries out corneal nerve.Traditional mating plate microscope use respectively two at an angle of 90 degrees
Object lens illuminated and be imaged, the imaging for cornea nerve is simultaneously not suitable for, so the present invention is designed using single-lens
Mating plate microscope be suitable for corneal nerve imaging.
The present invention is used for the mating plate microscope of corneal nerve imaging, including control device, illumination path, image obtain light
Road.The illumination path injects light into eye cornea, is formed at eye cornea and horizontal dynamic mating plate at α angle.Image letter
Number optical path is obtained into image with horizontal at angle β emit, described image obtains optical path and picture signal is sent into control device imaging.Its
In, the angle between the angle α and the angle β is 90 degree, and the angle α is not equal to 90 degree.The present invention replaces copolymerization burnt aobvious using the illumination of dynamic mating plate
Spot scan illumination in micro mirror, accelerates image taking speed, reduces shooting time.Also, light is not emitted directly toward eyeground by illumination path,
Injury of the illumination light to eyes can be reduced.
Specifically, mating plate microscope includes laser light source, the first lens group, reflection microscope group, the second lens group, camera sensing
Device.The laser light source transmitting light successively enters eye cornea through first lens group, the reflection microscope group, forms illumination light
Road.Picture signal successively focuses on the camera sensor through the reflection microscope group, second lens group, forms image and obtains
Optical path.
The control device includes control computer and control circuit.The control computer provides human-computer interaction
Interface, for laser lighting wavelength, the parameters such as power to be arranged；Laser scanning speed and angle are controlled, control camera obtains image,
And command adapted thereto is issued to control circuit.The control circuit effect is after converting computer instruction to analog signal to control
Continuous circuit, and the signal passed back by camera is received, computer is fed back to, forms real-time image on a display screen.
Fig. 4 shows a mating plate microscopical embodiment of the present invention for corneal nerve imaging.The reflection microscope group
Including two points of mirrors 36, object lens 38, reflecting mirror 39.Second lens group includes straight tube lens 37, filter 310.The laser light
Source 34 emits light after the first lens group 35, and You Erfen mirror 36 is reflected into object lens 38, then vertically injects reflecting mirror 39, passes through
Reflecting mirror 39 horizontally enters into eye cornea after reflecting, that is, forms horizontal mating plate.That is, the illumination path injects light into eye
Portion's cornea, it is zero degree that shape is at α angle at eye cornea.Picture signal is returned to horizontal project at an angle of 90 degrees (angle β is an angle of 90 degrees)
Object lens 38 enter sleeve lens 37 by two points of mirrors 36, are focused on camera sensor 311 by filter 310.The reflecting mirror
39 be camera lens front mirror, as shown in fig. 6, the reflecting mirror and level be at 45 degree of angles, generally by can after being connected with annulus
On object lens used in being fixed on.
Fig. 5 shows a certain example of first lens group, and first lens group includes amplifying lens group 351, column
Shape lens 352, uniaxial scanning galvanometer 353, lens group 354.The single shaft scanning galvanometer 353 can be X-axis, Y-axis, Z axis scanning
Galvanometer.The laser light source 34 emits light after the amplification of amplifying lens group, collimation, forms mating plate through the focusing of cylindrical lenses 352, makes
The mating plate of different depth is formed with uniaxial scanning galvanometer 353.Under another example, first lens group include amplifying lens,
Twin shaft scanning galvanometer, lens group.The twin shaft scanning galvanometer uses X-axis and Z axis scanning galvanometer, and wherein Y-axis is injected according to light
Eye direction is defined.The laser light source 34 emits light after the amplification of amplifying lens group, collimation, is formed through twin shaft scanning galvanometer
The mating plate of different depth.The amplifying lens group can be used one or more pieces lens and constitute the lens group with enlarging function.Institute
Stating lens group can be used one or more pieces lens, match with the scanning galvanometer, when scanning galvanometer carries out on different axis
After laser scanning, light is sent into two points of mirrors after scanning galvanometer by the lens group.
Fig. 2 shows the optical paths under embodiment described in Fig. 4.After illumination path 223 horizontally enters into eyeball 221, image letter
Breath 222 obtains optical path by the image of vertical direction and obtains.This mode illumination light will not direct projection eyeground, illumination light can be reduced to eye
The injury of eyeball.
Fig. 7 shows mating plate microscopical another embodiment of the present invention for corneal nerve imaging.Described first thoroughly
Microscope group 54 includes cylindrical lenses.The reflection microscope group includes polygon scarnning mirror instrument 55, lens 56, object lens 57.The laser light source
53 transmitting light enter the lens 56 by polygon 55 reflected light of scarnning mirror instrument after first lens group 54 focusing, later
The object lens 57 are horizontally entered into, most form the dynamic with level angled (e.g., the angle α is 45 degree of angles) at eye cornea finally
Mating plate.Picture signal and level angled (such as angle β is 135 degree of angles) project and return to object lens 57, successively pass through the lens
56, the polygon scarnning mirror instrument 55 enters second lens group after being reflected by the polygon scarnning mirror instrument 55.Described second thoroughly
Example shown in Fig. 8 can be used in microscope group 59, after such as using two lens 591,592, picture signal to pass through lens 591, by lens 592
It focuses on camera sensor.
Fig. 3 shows the optical path under embodiment described in Fig. 7.After the angled entrance eyeball 221 of illumination path 233,
Image information 222 is obtained by obtaining optical path with the image of illumination path vertical direction.In this fashion, the angle α is not limited to 45 degree of angles,
The angle β is not limited to 135 degree.
Reduce eyes of patients discomfort while shooting depth to increase, the laser light source is to emit swashing near infrared light
Radiant.The optical maser wavelength of selection, it should which near infrared wavelength region, not only penetration depth is longer, but also since human eye is to this
The light of wave band is insensitive, can reduce the uncomfortable degree of patient, for example, wavelength is about 700 nm to about 1100 nm.However, answering
This is note that the laser illuminator of 400-700 range is applied equally to the device.The laser light source is by optical fiber or directly beats
Out after laser, subsequent optical path is entered by the first lens group.Wherein, when being exported by fiber coupling, fiber type can be
Single mode or multimode.
Camera lens used in currently used Heidelberg is 63X times of Zeiss, the hydroscope that NA is 0.95, equally in embodiment
In, it is suitable for the above two design device, shooting time and relevant parameter is calculated so that Zeiss is with money object lens as an example, because using same
Money object lens, resolution ratio be it is identical, the main distinction is in image taking speed.The scanning speed of laser scanning mirror usual first at least can be with
Reach 500Hz, the mating plate secondly formed forms illumination mating plate of corresponding size according to used camera lens, with the exposure of 5-10ms
Time calculates, so per second can be imaged 98-192 images, so being limited only in the speed of the acquisition image of current camera.Phase
12-24 times is higher by than 8 image taking speeds per second in current Laser Scanning Confocal Microscope.It is clapped to largely reduce patient
The time is taken the photograph, the time of contact of its eyeball and object lens is reduced.Then, it should be noted that other amplification factors see cornea mind enough
The object lens of warp are also applied for the device.
In embodiments, the present invention further includes axicon lens for the mating plate microscope of corneal nerve imaging, is set to described sharp
Between radiant and first lens group.Laser light source, which emits light, to form Bezier by using the axicon lens of certain angle
Light, as shown in figure 9, gauss laser 72 forms Bezier light 73 after entering conical mirror 71 in parallel, the linear type of focusing is advantageous
In the bigger mating plate of generation, and increase imaging depth.This is suitable for both the above design scheme.
In embodiments, ophthalmically acceptable rubber cement is used between object lens and eyeball, avoids direct contact with and eyeball is damaged.
It should be understood by those skilled in the art that foregoing description and the embodiment of the present invention shown in the drawings are only used as illustrating
And it is not intended to limit the present invention.The purpose of the present invention completely effectively realizes.Function and structural principle of the invention is in reality
It applies and shows and illustrate in example, under without departing from the principle, embodiments of the present invention can have any deformation or modification.
Claims (10)
1. for the mating plate microscope of corneal nerve imaging, including control device, illumination path, image obtain optical path, feature
It is, the illumination path injects light into eye cornea, is formed at eye cornea and horizontal dynamic mating plate at α angle；Image
Signal and horizontal at angle β emit obtain optical path into image, and described image obtains optical path and picture signal is sent into control device imaging；
Wherein, the angle between the angle α and the angle β is 90 degree, and the angle α is not equal to 90 degree.
2. the mating plate microscope according to claim 1 for corneal nerve imaging, which is characterized in that further include laser light
Source, the first lens group, reflection microscope group, the second lens group, camera sensor；The laser light source transmitting light is successively through described first
Lens group, the reflection microscope group enter eye cornea, form illumination path；Picture signal is successively through the reflection microscope group, described
Second lens group focuses on the camera sensor, forms image and obtains optical path.
3. the mating plate microscope according to claim 2 for corneal nerve imaging, which is characterized in that first lens
Group includes cylindrical lenses；The reflection microscope group includes polygon scarnning mirror instrument, lens, object lens；The laser light source transmitting light is through institute
It states and the lens is entered by the polygon scarnning mirror instrument reflected light after cylindrical lenses focus, horizontally enter into the object lens later, most
Finally it is formed at eye cornea and the horizontal dynamic mating plate at 45 degree of angles；Picture signal and horizontal project at 135 degree of angles return to object
Mirror successively passes through the lens, the polygon scarnning mirror instrument, by entering second lens after the polygon scarnning mirror instrument reflection
Group.
4. the mating plate microscope according to claim 2 for corneal nerve imaging, which is characterized in that the reflection microscope group
Including two points of mirrors, object lens, reflecting mirrors；After first lens group, You Erfen mirror is reflected into the laser light source transmitting light
Object lens then vertically inject reflecting mirror, horizontally enter into eye cornea after reflecting by reflecting mirror；Picture signal and level are at 90 degree
Angle is projected and returns to object lens, enters second lens group by two points of mirrors.
5. the mating plate microscope according to claim 4 for corneal nerve imaging, which is characterized in that first lens
Group includes amplifying lens group, cylindrical lenses, uniaxial scanning galvanometer, lens group.
6. the mating plate microscope according to claim 4 for corneal nerve imaging, which is characterized in that first lens
Group includes amplifying lens group, twin shaft scanning galvanometer, lens group.
7. it is according to claim 4 for corneal nerve imaging mating plate microscope, which is characterized in that the reflecting mirror with
Level is fixed on the object lens at 45 degree of angles.
8. the mating plate microscope according to claim 1 for corneal nerve imaging, which is characterized in that the laser light source
For the laser light source for emitting near infrared light.
9. the mating plate microscope according to claim 8 for corneal nerve imaging, which is characterized in that the laser light source
The wavelength for emitting light is 400-1100nm.
10. the mating plate microscope according to claim 1 for corneal nerve imaging, which is characterized in that it further include axicon lens,
Between the laser light source and first lens group, the laser light source transmitting light forms Bezier after the axicon lens
Light enters first lens.
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Application publication date: 20190517 |
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