CN106361266B - Super-resolution confocal ophthalmoscope based on pupil filter and dark field technology - Google Patents
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Abstract
The invention discloses a super-resolution confocal ophthalmoscope based on a pupil filter and a dark field technology, which can accurately obtain super-resolution and dark field images of retina of human eyes of a living body in real time. The beacon light source corrects the aberration of the human eyes; the imaging light source obtains a human eye image. According to Rayleigh criterion, representing resolution by using full width at half maximum, adding a two-zone type phase pupil filter at an illumination end, and taking the size of Airy spots from a pinhole; when filters are added at the imaging end or both ends, the pinhole takes 1.5 times of airy disk, and the diffraction limit condition that the transverse half-height width is smaller than that of the common microscope pinhole when the airy disk is taken can be realized, so that super-resolution is realized to obtain a super-resolution image. On the basis, translating the big and small eye holes by an eye patch distance; and (3) carrying out central blocking or linear blocking on the pinholes which are 1.5 times of the airy spots in size, so that dark field imaging can be realized.
Description
Technical Field
The invention relates to a medical imaging diagnosis system for imaging retina, in particular to a super-resolution confocal ophthalmoscope based on a pupil filter and a dark field technology.
Background
The retina is a membrane with a thickness of about 300 microns, which is positioned on the fundus of the eye of a human eye and comprises a plurality of layers, such as a nerve fiber layer, a nerve cell layer, a blood vessel layer, an optic cell layer, a melanin epithelial cell layer and the like. The retina of the human eye is important information indispensable in ophthalmic diagnosis and treatment, and the real-time tracking of detail changes of the retina of the eye fundus can help early diagnosis and prevention of body diseases.
In 1987, r.h. webb applied confocal scanning techniques to the retina of a living human eye. Since the living human eye is equivalent to an optical system and has various aberrations, the resolution and contrast of retina imaging are greatly limited, and the characteristics of the fundus can not be distinguished on the visual cell scale.
The adaptive optics technology is a new technology developed in the 70 s, and originally compensates and corrects an observed target by detecting the distortion of the wave front disturbance caused by the atmospheric turbulence. In 1994, Liang et al developed a wavefront sensor for the human eye based on the artmann-Shack principle. In 2001, the research groups of the university of Murcia and the university of Rochester realized closed-loop correction of dynamic aberrations of the fundus camera in the laboratory one after the other. In 2002, Austin Roorda et al developed the first adaptive optics confocal ophthalmoscope at Houston university.
Dark field illumination in fourier optics refers to the removal of zero order light and the remaining light, i.e., the removal of background light to produce an image showing details. By adjusting the pinhole of the confocal microscope, there are several ways to achieve the dark field mode. In 1982, i.j. cox proposed translating the pinhole by the airy disk radius size to obtain a dark field image of the target. In 1998, Akitoshi Yoshida obtained dark field images in the modified confocal microscope by center masking the confocal pinhole.
In 1952, Toraldo introduced the concept of super-resolution for the first time into optics, and a diffractive device placed at the pupil modulated the light field to some specific distribution, with the main lobe size of the system PSF below the diffraction limit, and only lower side lobes around the main lobe appeared. Super-resolution techniques have long been used in confocal scanning imaging systems, 1996, Min Gu proposed that when imaging a sample behind a highly scattering medium, a pinhole of an ideal pinhole size could not be used, and an annular pupil could be used at the illumination end, a high resolution effect close to that of the ideal pinhole in the lateral direction could be achieved. Yusufu and alfedeo Dubra et al in 2012 adopt a central shading method on the pupils of the illumination end and the imaging end of the adaptive confocal ophthalmoscope, thereby forming an annular pupil to realize super-resolution imaging of the retina of a human eye.
The method has the advantages of simple operation, but has some defects:
due to the adoption of the center shielding mode, the light intensity is greatly reduced, and an image with high signal-to-noise ratio cannot be obtained. The super-resolution image under the condition of only one filter can be obtained each time, the efficiency is low, and the comparison is inconvenient.
Disclosure of Invention
The technical problem to be solved by the invention is as follows: in a common self-adaptive confocal ophthalmoscope, the horizontal full width at half maximum of the PSF cannot be further reduced due to the limitation of diffraction limit; since only one image can be obtained at a time and no dark-field image can be obtained, the efficiency is low and no more detailed information of the retina can be obtained. Aiming at the defects, the phase pupil filter is applied to the self-adaptive confocal ophthalmoscope, so that the full width at half maximum of the PSF can be effectively reduced under the condition of reducing less light intensity; adjusting the pinhole to obtain a dark field image displaying more details; two sets of photoelectric detection systems are adopted, so that the efficiency is improved, and the comparison is convenient.
The technical scheme adopted by the invention is as follows: a super-resolution confocal ophthalmoscope based on a pupil filter and a dark field technology comprises a beacon light source, an imaging light source, a lighting end pupil filter, a two-dimensional scanning galvanometer, a deformable mirror, a first optical filter, a Hartmann sensor, a second optical filter, a first imaging end phase type pupil filter, a first pinhole, a first photomultiplier, a second imaging end phase type pupil filter, a second pinhole and a second photomultiplier, wherein,
the light of the beacon light source reaches human eyes after passing through the two-dimensional scanning galvanometer and the deformable mirror, reaches the Hartmann sensor after being reflected through the deformable mirror, the two-dimensional scanning galvanometer and the first optical filter, and is calculated to obtain wavefront disturbance, so that the deformable mirror is controlled to correct aberration;
the light of the imaging light source reaches human eyes after passing through a pupil filter at an illumination end, a two-dimensional scanning galvanometer and a deformable mirror, is divided into two beams of light after being reflected by the deformable mirror, the two-dimensional scanning galvanometer and a second light filter, and two human eye images are obtained respectively at a first photomultiplier and a second photomultiplier after passing through a first imaging end phase type pupil filter or a second imaging end phase type pupil filter and a first pinhole or a second pinhole, and the distribution function of the illumination end filter is h1(v, u) represents that the distribution function of the imaging end filter can be all expressed by h2(v, u) wherein the point spread function of any path can be expressed asThe resolution can be represented by obtaining the transverse full width at half maximum through a point spread function, wherein 1, when a pupil filter at an illumination end is added at the illumination end, the radius of the first pinhole or the second pinhole is the size of the Airy spot; 2. adding only the first imaging end phase type pupil filter and the first pinhole to obtain 1.5 times of Airy spots orOnly adding a second imaging end phase-type pupil filter and a second pinhole to obtain 1.5 times of airy disc; 3. after the illumination end is added with an illumination end pupil filter, adding a first imaging end phase type pupil filter and a first pinhole to take 1.5 times of the airy spots or adding a second imaging end phase type pupil filter and a second pinhole to take 1.5 times of the airy spots; the three conditions can enable the transverse half-height width to be smaller than the diffraction limit condition when the common microscope pinhole takes the airy disk size, so that super-resolution is achieved, a super-resolution image is obtained, on the basis, the airy disk size pinhole is translated by an airy disk distance, and center blocking or linear blocking is carried out on the 1.5 times of the airy disk size pinhole, so that dark field imaging can be achieved.
Furthermore, the first optical filter only allows the beacon light to pass through, so that the aberration of human eyes is detected; the second filter only allows imaging light to pass through, so that a retina image of a human eye is obtained.
Furthermore, the beacon light source, the human eyes and the Hartmann sensor form an independent light path and are not influenced by the addition of a pupil filter and a dark field technology, so that the real-time detection and correction of the aberration of the human eyes are ensured, and the image resolution and the contrast are improved.
Further, the super-resolution effect and the image light intensity are related to the relative radius of the illumination end pupil filter and the first imaging end phase type pupil filter and the second imaging end phase type pupil filter, and in the case that the relative radius is less than 0.4, the larger the radius, the better the super-resolution effect is, but the lower the image light intensity is.
Furthermore, the first imaging end phase type pupil filter, the first pinhole, the first photomultiplier tube, the second imaging end phase type pupil filter, the second pinhole and the second photomultiplier tube respectively form two sets of photoelectric detection systems, and the super-resolution image and the dark field image of the retina can be obtained simultaneously.
Compared with the prior art, the invention has the advantages that:
1. the invention has better super-resolution capability, can effectively reduce the half-height width of a transverse point spread function, improves the intensity of high-frequency components, and obtains more detailed images of human retina.
2. The invention has little influence on the signal intensity and the signal-to-noise ratio, the pupil filter at the imaging end adopts a two-region phase filter, and the light intensity signal of more than 90 percent of the original signal can be obtained along with the increase of the pinhole.
3. The pupil filter and the pinhole change only affect the transmission of imaging light rays and do not affect the beacon light path, so that the aberration of human eyes can be detected and corrected in real time.
4. The invention has two sets of photoelectric detection systems, and can simultaneously obtain super-resolution and dark field images.
Drawings
FIG. 1 is a schematic diagram of a super-resolution confocal ophthalmoscope structure based on a pupil filter and dark field technology; in fig. 1, 1 is a beacon light source, 2 is an imaging light source, 3 is an illumination end pupil filter, 4 is a two-dimensional scanning galvanometer, 5 is a deformable mirror, 6 is a human eye, 7 is a first optical filter, 8 is a hartmann wavefront sensor, 9 is a second optical filter, 10 is a first imaging end phase type pupil filter, 11 is a first pinhole, 12 is a first photomultiplier, 13 is a second imaging end phase type pupil filter, 14 is a second pinhole, and 15 is a second photomultiplier.
FIG. 2 is a schematic diagram of super-resolution performance index; in FIG. 2 rsRadius of main lobe in focal plane of PSF for super resolution, rLRadius of diffraction limit, IsCentral intensity of super-resolution PSF, ILCentral intensity of diffraction-limited PSF, IMThe highest side lobe intensity of the super-resolution PSF.
FIG. 3 is an image of the half-height width of the transverse PSF of the system varying with the size of the pinhole after phase-type pupil filters of different radii are added at both ends; in fig. 3 p is the filter relative radius.
FIG. 4 is a schematic diagram of translating a pinhole to achieve dark field imaging.
FIG. 5 is a schematic diagram of dark field imaging with pinhole center occlusion.
Detailed Description
The invention is described in detail below with reference to the figures and the detailed description.
As shown in fig. 1, the super-resolution confocal ophthalmoscope based on the pupil filter and dark field technology of the present invention is composed of a beacon light source 1, an imaging light source 2, an illumination end pupil filter 3, a two-dimensional scanning galvanometer 4, a deformable mirror 5, a first optical filter 7, a hartmann sensor 8, a second optical filter 9, a first imaging end phase-type pupil filter 10, a first pinhole 11, a first photomultiplier 12, a second imaging end phase-type pupil filter 13, a second pinhole 14, and a second photomultiplier 15.
The working process of the super-resolution optical confocal ophthalmoscope of the present example is as follows:
the light of the beacon light source 1 reaches human eyes 6 after passing through the two-dimensional scanning galvanometer 4 and the deformable mirror 5, reaches the Hartmann sensor 8 after being reflected through the deformable mirror 5, the two-dimensional scanning galvanometer 4 and the first optical filter 7, and is subjected to calculation to obtain wavefront disturbance, so that the deformable mirror 5 is controlled to correct aberration;
the light of the imaging light source 2 passes through the pupil filter 3 at the illumination end, the two-dimensional scanning galvanometer 4 and the deformable mirror 5, then reaches the human eyes 6, is reflected, then passes through the deformable mirror 5, the two-dimensional scanning galvanometer 4 and the second optical filter 9, is divided into two beams of light, and passes through the first imaging end phase type pupil filter 10 or the second imaging end phase type pupil filter 13 and the first pinhole 11 or the second pinhole 14, and then two human eye images are obtained at the first photomultiplier 12 and the second photomultiplier 15 respectively.
As shown in fig. 2, the pupil super-resolution filter modulates the light field to a particular distribution, and the PSF of the imaging system can produce a zero intensity spot at a pre-specified location on the focal plane, such that the size of the main lobe is below the diffraction limit and only lower side lobes are present in a limited area around the main lobe.
The pupil function after adding the two-zone type phase pupil filter is as follows:
wherein, the independent variable rho is a radius value, a small circle at the center of the filter is p, and the phase difference between the two areas is p
When in useWhen the value is pi, the parameter G is rL/rsThe increase is the fastest and the most rapid,
the pinhole of the confocal ophthalmoscope is circular and is a function of:
wherein v isdIs the pinhole radius.
After the pupil filter is added into the confocal ophthalmoscope, the formula of the point spread function finally obtained is as follows:
wherein,
wherein h is1(v, u) and h2(v, u) are pupil distribution functions of the illumination end and the imaging end after the phase type pupil filter is added. P1(P) and P2(ρ) are the filter functions of the illumination and imaging ends, respectively, v and u characterize the transverse and axial coordinates, respectively, and x, y and z are the coordinates of the three directions, respectively.
The method is substituted into an original expression, and at the moment, the expressions of the transverse distribution function, the axial distribution function and the light intensity function of the system PSF can be obtained.
Transverse distribution:
axial distribution:
light intensity at zero point:
wherein h is1(v, u) and h2(v, u) are pupil distribution functions of an illumination end and an imaging end respectively after the phase type pupil filter is added, v and u represent transverse and axial coordinates respectively, vdIs the pinhole radius.
The resolution can be characterized by obtaining the full width at half maximum according to a Rayleigh criterion.
Therefore, an image of the PSF with half-height width varying with the pinhole radius can be obtained after the phase type pupil filter is added. Taking the example of adding phase filters at both ends, as shown in fig. 3, after the filters are added, the PSF horizontal full width at half maximum is reduced to a certain extent, and the larger the radius, the larger the change caused by the filters.
The result shows that when the two-region phase filter is added at the illumination end, the pinhole radius is the size of the Airy spots; when the filter is added at the imaging end or the filters are added at the two ends simultaneously, the pinhole takes 1.5 times of airy disk, and the three conditions can enable the transverse half-height width to be smaller than the diffraction limit condition when the airy disk is taken by the pinhole of a common microscope, so that super-resolution is realized, and a super-resolution image is obtained.
In the image, the high frequency component corresponds to the details of the image, the details of human eyes have very important roles in the prevention, diagnosis and treatment of diseases, and the details in the retina can be obtained through the dark field image.
And transforming the pinhole, and removing zero-order background light to obtain a dark field image.
One method is to translate a pinhole of airy disk size as shown in figure 4. The relationship expression of the intensity of the zero-order light and the translation distance at this time is as follows:
wherein,is the translation distance of the pinhole, J1Is a first order Bessel function;
when in useTaking 3.83 promptlyWhen the radius of the spot is large, the intensity of the zero-order light becomes 0, and a dark field image can be obtained.
Another approach is to center-mask or line-mask the confocal pinhole as shown in fig. 5. This can block the direct reflected light and obtain only the multiple scattered light, thereby obtaining a dark field image.
Therefore, the big and small holes of the Airy spots are translated by an Airy spot distance, and the central blocking or linear blocking is carried out on the big and small holes of the 1.5 times of the Airy spots, so that the dark field imaging can be realized.
Thus, a super-resolution confocal ophthalmoscope based on a pupil filter and a dark field technology can be realized.
Claims (5)
1. A super-resolution confocal ophthalmoscope based on a pupil filter and a dark field technology is characterized in that: comprises a beacon light source (1), an imaging light source (2), a lighting end pupil filter (3), a two-dimensional scanning galvanometer (4), a deformable mirror (5), a first optical filter (7), a Hartmann sensor (8), a second optical filter (9), a first imaging end phase type pupil filter (10), a first pinhole (11), a first photomultiplier (12), a second imaging end phase type pupil filter (13), a second pinhole (14) and a second photomultiplier (15), wherein,
the light of the beacon light source (1) reaches a human eye (6) after passing through the two-dimensional scanning galvanometer (4) and the deformable mirror (5), reaches the Hartmann sensor (8) after being reflected after passing through the deformable mirror (5), the two-dimensional scanning galvanometer (4) and the first optical filter (7), and is subjected to calculation to obtain wavefront disturbance, so that the deformable mirror (5) is controlled to correct aberration;
the light of an imaging light source (2) reaches human eyes (6) after passing through an illumination end pupil filter (3), a two-dimensional scanning galvanometer (4) and a deformable mirror (5), after being reflected, the light passes through the deformable mirror (5), the two-dimensional scanning galvanometer (4) and a second optical filter (9) and is divided into two beams of light, one beam of light sequentially passes through a first imaging end phase type pupil filter (10) and a first pinhole (11), the other beam of light sequentially passes through a second imaging end phase type pupil filter (13) and a second pinhole (14), then two human eye images are obtained on a first photomultiplier (12) and a second photomultiplier (15) respectively, and the distribution function of the illumination pupil end pupil filter is h1(v, u) represents that the distribution functions of the first imaging end phase type pupil filter and the second imaging end phase type pupil filter can be h2(v, u) represents that the point spread function of any one of the paths through which the two beams pass can be expressed asThe resolution can be represented by obtaining the transverse full width at half maximum through a point spread function, wherein in case 1, when the illumination end pupil filter (3) is added at the illumination end, the radius of the first pinhole (11) or the second pinhole (14) takes the size of an airy disk, and at the moment, the first imaging end phase type pupil filter (10) and the second imaging end phase type pupil filter (13) are not added; in case 2, only the first imaging end phase type pupil filter (10) is added, the first pinhole (11) takes 1.5 times of airy disc, or only the second imaging end phase type pupil filter (13) is added, and the second pinhole (14) takes 1.5 times of airy disc, at this time, the illumination end pupil filter (3) is not added; 3, after an illumination end pupil filter (3) is added at an illumination end, a first imaging end phase type pupil filter (10) is added, wherein 1.5 times of Airy spots are taken by a first pinhole (11), or a second imaging end phase type pupil filter (13) is added, and 1.5 times of Airy spots are taken by a second pinhole (14); in three cases, the transverse half-height width of the needle can be smaller than that of the common microscope when the size of the Airy spots is taken from the pinholeAnd (3) diffraction limit condition, so that super-resolution is realized to obtain a super-resolution image, the large and small holes of the Airy spots are translated by an Airy spot distance, and central blocking or linear blocking is carried out on the large and small holes of the 1.5 times of the Airy spots, so that dark field imaging can be realized.
2. A super-resolution confocal ophthalmoscope based on pupil filter and dark field techniques according to claim 1, characterized in that: the first optical filter (7) only allows the beacon light to pass through, thereby detecting the aberration of human eyes; the second filter (9) allows only the imaging light to pass through, thereby obtaining a retinal image of the human eye.
3. A super-resolution confocal ophthalmoscope based on pupil filter and dark field techniques according to claim 1, characterized in that: the beacon light source (1), the human eyes (6) and the Hartmann sensor (8) form an independent light path and are not influenced by the addition of a pupil filter and a dark field technology, so that the real-time detection and correction of the aberration of the human eyes are ensured, and the image resolution and the contrast are improved.
4. A super-resolution confocal ophthalmoscope based on pupil filter and dark field techniques according to claim 1, characterized in that: the super-resolution effect and the image light intensity are related to the relative radius of the illumination end pupil filter (3) and the first imaging end phase type pupil filter (10) and the second imaging end phase type pupil filter (13), and under the condition that the relative radius is less than 0.4, the larger the radius, the better the super-resolution effect is, but the lower the image light intensity is.
5. A super-resolution confocal ophthalmoscope based on pupil filter and dark field techniques according to claim 1, characterized in that: the first imaging end phase type pupil filter (10), the first pinhole (11), the first photomultiplier (12), the second imaging end phase type pupil filter (13), the second pinhole (14) and the second photomultiplier (15) respectively form two sets of photoelectric detection systems, and the super-resolution image and the dark field image of the retina can be obtained simultaneously.
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| CN103431845B (en) * | 2013-08-28 | 2015-08-05 | 北京信息科技大学 | Based on optical coherence chromatography imaging method and the device of radial polarized light beam |
| CN103815867B (en) * | 2014-02-26 | 2015-09-30 | 中国科学院光电技术研究所 | Continuously adjustable optical coherence tomography instrument with annulus illumination retina dark field |
| CN104352214B (en) * | 2014-11-13 | 2016-03-30 | 中国科学院光电技术研究所 | Wavefront modulation dark field self-adaptive optics retina imager |
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