CN106361266A - Super-resolution confocal ophthalmoscope based on optical pupil filter and dark field technique - Google Patents

Abstract

The invention discloses a super-resolution confocal ophthalmoscope based on an optical pupil filter and a dark field technique. The super-resolution confocal ophthalmoscope is capable of accurately acquiring super-resolution dark field images of retinas of living human eyes in real time, and comprises a beacon light source, an imaging light source, an optical pupil filter, a two-dimensional scanning galvanometer, a Hartmann sensor, a deformable mirror, an optical filter and a photoelectric detection system. The beacon light source is used for correcting human eye aberrations; the imaging light source is used for acquiring human eye images. The operating method comprises the following steps: characterizing resolution according to Rayleigh criterion by using full width at half maximum, adding a two-zone type phase optical pupil filter at an illumination end, wherein the pinhole is equal to Airy disk size; allowing the pinhole to be equal to 1.5 times that of Airy disk size when the filter(s) is/are arranged at the imaging end or two ends, so that the diffraction limit condition can be realized when the transverse full width at half maximum is less than the pinhole of a general microscope equal to the Airy disk size, and the super-resolution image can be acquired at a super-resolution ratio. On the basis, the pinhole equal to the Airy disk size is translated by an Airy disk distance, the pinhole equal to 1.5 times that of the Airy disk size is subjected to central blocking or linear blocking, so that dark field imaging can be realized.

Description

A kind of super-resolution confocal ophthalmoscope based on iris filter and dark field method

Technical field

The present invention relates to a kind of for medical imaging diagnostic system that retina is imaged and in particular to one kind is based on The super-resolution confocal ophthalmoscope of iris filter and dark field method.

Background technology

Retina is in the film of about 300 microns of the thick layer on human eye optical fundus, and it includes nerve fibre layer, neurocyte The multiple structures such as layer, vascular lamina, visual cell layer and melanin epithelium layer.Human eye retina be ophthalmic diagnosis and treatment in not The important information that can or lack, the variations in detail of real-time tracking eye ground will be helpful to early diagnosiss of body illness and pre- Anti-.

1987, cofocus scanning technology was applied to living human eye retina image-forming by r.h.webb.Due to living human eye phase When in an optical system, there are various aberrations, lead to the resolution of retina image-forming and contrast be very limited it is impossible to Visual cell yardstick is differentiated to optical fundus feature.

Adaptive optical technique is the new technique just having developed the seventies, is by atmospheric sounding turbulent flow, wavefront to be disturbed originally Move the distortion causing and then rectification is compensated to observed object.1994, liang et al. have developed one kind and is based on artmann- The wave front detector being applied to human eye of shack principle.Calendar year 2001, murcia university and rochester university research group are first Afterwards experiment interior achieve fundus camera dynamic aberration closed-loop corrected.2002, austin roorda et al. existed Houston university develops the confocal ophthalmoscope of First adaptive optics.

Dark-ground illumination, in terms of Fourier Optics, refers to that removing zeroth order light leaves other light, that is, remove bias light from And obtain showing the image of details.By being adjusted to the pin hole of confocal microscope, can there are multiple dark field modes of realizing Method.Nineteen eighty-two, i.j.cox proposes for pin hole to translate an Airy disk radius size, you can obtain the darkfield image of target. 1998, akitoshi yoshida, by carrying out central obscuration to confocal pinhole, obtained in improved confocal microscope Darkfield image.

Nineteen fifty-two, the concept of super-resolution is introduced optics by toraldo first, and light field is adjusted by the diffractive optical element being placed on pupil It is made as certain special distribution, the main lobe size of system psf is less than diffraction limit, around main lobe, relatively low secondary lobe only occurs. Also long-standing using super resolution technology in confocal scanning imaging system, 1996, min gu proposed after to high scattering material Sample imaging when, when pin hole cannot can adopt annular pupil in illumination end using preferable aperture size, equally can reach near Horizontal high-resolution effect in preferable pin hole.Yusufu and alfredo dubra in 2012 et al. is in the confocal ophthalmoscope of self adaptation Illumination end and imaging end pupil on using central shielding method, thus forming annular pupil to realize the super of human eye retina Resolution imaging.

The advantage of this method be operate easier, but there is also some shortcomings:

Due to employing the mode of central shielding, so light intensity can greatly reduce it is impossible to obtain the very high image of signal to noise ratio. Can only obtain the super resolution image under a kind of filter conditions every time, less efficient and be inconvenient to compare.

Content of the invention

The technical problem to be solved in the present invention is: the confocal ophthalmoscope of common self adaptation, due to the restriction of diffraction limit, The horizontal halfwidth of psf can not reduce further；Due to can only obtain a sub-picture every time and darkfield image, efficiency cannot being obtained More details information relatively low and that retina cannot be obtained.Not enough for these, phase place iris filter is applied to by the present invention In the confocal ophthalmoscope of self adaptation, in the case of reducing less light intensity, can effectively reduce the halfwidth of psf；To pin hole It is adjusted, obtain showing darkfield image in greater detail；Using two sets of Photodetection systems, improve efficiency and convenient contrast.

The technical solution used in the present invention is: a kind of super-resolution confocal inspection eye based on iris filter and dark field method Mirror, including beacon light source, imaging source, illumination end iris filter, two-dimensional scanning mirrors, distorting lenss, the first optical filter, Hart Graceful sensor, the second optical filter, the first imaging end Phase only pupil filters, the first pin hole, the first photomultiplier tube, the second one-tenth Picture end Phase only pupil filters, the second pin hole and the second photomultiplier tube, wherein,

The light of beacon light source reaches human eye after two-dimensional scanning mirrors and distorting lenss, after reflection again through distorting lenss, Two-dimensional scanning mirrors and the first optical filter reach Hartmann sensor, are calculated Wavefront Perturbation, thus controlling distorting lenss to correct Aberration；

The light of imaging source reaches human eye after the iris filter of illumination end, two-dimensional scanning mirrors and distorting lenss, Through distorting lenss, two-dimensional scanning mirrors and the second optical filter after reflection, it is further divided into two-beam, through the first imaging end phase type light After pupil wave filter or the second imaging end Phase only pupil filters and the first pin hole or the second pin hole, respectively in the first photoelectricity times Increase pipe and the second photomultiplier transit is in control two width eye images, illuminate end filter distribution function h₁(v, u) represents, is imaged end End filter distribution function all can use h₂(v, u) represents, the point spread function on wherein any one road is all represented byHorizontal halfwidth can be obtained by point spread function and characterize resolution Rate, wherein, 1, only when illumination end adds illumination end iris filter, the first pin hole or the second pin hole radius take Airy disk big Little；2nd, the first imaging end Phase only pupil filters and the first pin hole is only added to take 1.5 times of Airy disks or only add the second imaging End Phase only pupil filters and the second pin hole take 1.5 times of Airy disks；3rd, after illumination end adds illumination end iris filter, then plus Enter the first imaging end Phase only pupil filters and the first pin hole takes 1.5 times of Airy disks or adds the second imaging end phase type Iris filter and the second pin hole take 1.5 times of Airy disks；Three kinds of situations all can make horizontal halfwidth be less than simple microscope pin hole Take diffraction limit situation during Airy disk size, thus realizing super-resolution to obtain super resolution image, on this basis, to Airy disk Size pin hole translates an Airy disk distance, carries out central obscuration to 1.5 times of Airy disk size pin holes or wire is blocked, you can Realize dark-field imaging.

Further, the first optical filter only allows beacon light pass through, thus detecting human eye aberration；Second optical filter only allows into As light passes through, thus obtaining human eye retina's image.

Further, beacon light source, human eye and Hartmann sensor composition independent optical paths, be not subject to add iris filter and The impact of dark field method, thus ensureing real-time detection and correcting human eye aberration, improves image resolution ratio and contrast.

Further, super-resolution effect and image intensity and illumination end iris filter and the first imaging end phase type pupil Wave filter, the relative radius correlation of the second imaging end Phase only pupil filters, in the case that relative radius are less than 0.4, half Footpath bigger super-resolution effect is better, but image intensity is lower.

Further, the first imaging end Phase only pupil filters, the first pin hole, the first photomultiplier tube and the second imaging End Phase only pupil filters, the second pin hole, the second photomultiplier tube respectively constitute two sets of Photodetection systems it is ensured that permissible Obtain super resolution image and the darkfield image of retina simultaneously.

The present invention compared with prior art has the advantage, that

1st, the present invention has more preferable hyperresolution, can be effectively reduced the halfwidth of horizontal point spread function, improves The intensity of high fdrequency components, obtains the more details image of human eye retina.

2nd, for the impact very little of signal light intensity and signal to noise ratio, the iris filter being imaged end adopts two zone type phases to the present invention Position wave filter, with the increase of pin hole, can get the light intensity signal of original signal more than 90%.

3rd, the iris filter in the present invention and pin hole change only affect to be imaged the propagation of light, do not have for beacon light path Impact is it is possible to real-time detection correct human eye aberration.

4th, the present invention has two sets of Photodetection systems, can obtain super-resolution and darkfield image simultaneously.

Brief description

Fig. 1 is the super-resolution confocal ophthalmoscope structural representation based on iris filter and dark field method；In Fig. 1,1 is letter Mark light source, 2 is imaging source, and 3 is illumination end iris filter, and 4 is two-dimensional scanning mirrors, and 5 is distorting lenss, and 6 is human eye, and 7 are First optical filter, 8 is Hartmann wave front sensor, and 9 is the second optical filter, and 10 is the first imaging end Phase only pupil filters, 11 is the first pin hole, and 12 is the first photomultiplier tube, and 13 is the second imaging end Phase only pupil filters, and 14 is the second pin hole, 15 is the second photomultiplier tube.

Fig. 2 is super-resolution performance indications schematic diagram；R in Fig. 2_sFor the main lobe radius on focal plane for the psf of super-resolution, r_lFor The radius of diffraction limit, i_sFor the center intensity of super-resolution psf, i_lFor the center intensity of diffraction limit psf, i_mFor super-resolution psf Highest side lobe intensity.

Fig. 3 adds after the Phase only pupil filters of different radii for two ends, and the halfwidth of the horizontal psf of system is with pin hole The image of size variation；In Fig. 3, p is wave filter relative radius.

Fig. 4 is the schematic diagram that translation pin hole realizes dark-field imaging.

Fig. 5 realizes the schematic diagram of dark-field imaging for pin hole central shielding.

Specific embodiment

Below in conjunction with the accompanying drawings and specific embodiment is discussed in detail the present invention.

As shown in figure 1, a kind of super-resolution confocal ophthalmoscope based on iris filter and dark field method of the present invention, by beacon Light source 1, imaging source 2, illumination end iris filter 3, two-dimensional scanning mirrors 4, distorting lenss 5, the first optical filter 7, Hartmann pass Sensor 8, the second optical filter 9, first be imaged end Phase only pupil filters 10, the first pin hole 11, the first photomultiplier tube 12, the Two imaging end Phase only pupil filters 13, the second pin hole 14, the second photomultiplier tube 15 form.

The super-resolution optical confocal ophthalmoscope work process of this example is as follows:

The light of beacon light source 1 reaches human eye 6 after two-dimensional scanning mirrors 4 and distorting lenss 5, again through deformation after reflection Mirror 5, two-dimensional scanning mirrors 4 and the first optical filter 7 reach Hartmann sensor 8, are calculated Wavefront Perturbation, thus controlling deformation Mirror 5 aberration correction；

The light of imaging source 2 arrives intelligent after the iris filter 3 of illumination end, two-dimensional scanning mirrors 4 and distorting lenss 5 Again through distorting lenss 5, two-dimensional scanning mirrors 4 and the second optical filter 9 after eye 6, reflection, it is further divided into two-beam, through the first imaging End Phase only pupil filters 10 or the second imaging end Phase only pupil filters 13 and the first pin hole 11 or the second pin hole 14 Afterwards, two width eye images are obtained in the first photomultiplier tube 12 and the second photomultiplier tube 15 respectively.

As shown in Fig. 2 light field is modulated to certain special distribution by Pupil Super-Resolution wave filter, then the psf of imaging system Zero intensity point can be produced so that the size of main lobe is less than diffraction limit, around main lobe on focal plane in preassigned position Relatively low secondary lobe only occurs in finite region.

The pupil function after two zone type phase place iris filters is added to be:

Wherein, independent variable ρ is radius value, and filter center roundlet value is p, and the phase contrast in twoth area is

WhenWhen value is π, parameter g=r_l/r_sIncrease the fastest,

Confocal Oph pin hole is circle, and its function is:

Wherein v_dFor pin hole radius.

Iris filter is added after confocal ophthalmoscope, the formula of the point spread function finally giving is:

$h_c(v,u)=\left|h_1(v,u){|}^2\right|h_2(v,u){|}^2{\&circletimes;}_{3}d\left(v\right)---\left(3\right)$

Wherein,

$h_1(v,u)={\&integral;}_0^1{p}_1\left(\mathrm{\ρ}\right)\exp (-\frac{{\mathrm{iu\ρ}}^2}{2})j_0\left(v\mathrm{\ρ}\right)\mathrm{\ρ}d\mathrm{\ρ}---\left(4\right)$

$h_2(v,u)={\&integral;}_0^{b/a}{p}_2\left(\mathrm{\ρ}\right)\exp (-\frac{{\mathrm{iu\ρ}}^2}{2})j_0\left(v\mathrm{\ρ}\right)\mathrm{\ρ}d\mathrm{\ρ}---\left(5\right)$

$v=\frac{2\mathrm{\π}}{\mathrm{\λ}}\left(\frac{a}{f}\right)\sqrt{x^2+y^2},u=\frac{2\mathrm{\π}}{\mathrm{\λ}}{\left(\frac{a}{f}\right)}^{2}z---\left(6\right)$

Wherein, h₁(v, u) and h₂(v, u) is respectively the illumination end after adding Phase only pupil filters and the light at imaging end Pupil distribution function.p₁(ρ) and p₂(ρ) it is respectively illumination end and the filter function at imaging end, v and u characterizes laterally and axially respectively Coordinate, x, y and z are respectively the coordinate in three directions.

Carry it into former formula, now we can obtain the Transverse functions of system psf, axial distribution function and light The expression formula of strong function.

Cross direction profiles:

$i\left(v\right)=|h_1(v,0){|}^2\&lsqb;2\mathrm{\&pi;}{\&integral;}_0^{v_d-v}|h_2(t,0){|}^{2}tdt+2{\&integral;}_{v_d-v}^{v_d+v}|h_2(t,0){|}^2\arccos \left(\frac{t^2+v^2-{v_d}^2}{2tv}\right)tdt\&rsqb;,v<v_d$

$i\left(v\right)=2|h_1(v,u){|}^2\&lsqb;{\&integral;}_{v-v_d}^{v_d+v}|h_2(t,0){|}^2\arccos \left(\frac{t^2+v^2-{v_d}^2}{2tv}\right)tdt\&rsqb;,v>v_d---\left(7\right)$

Axially it is distributed:

$i\left(u\right)=|h_1(0,u){|}^2\&lsqb;2\mathrm{\&pi;}{\&integral;}_0^{v_d}|h_2(t,u){|}^{2}tdt\&rsqb;---\left(8\right)$

Zero point light intensity:

$i(0,0)=|h_1(0,0){|}^2\&lsqb;2\mathrm{\&pi;}{\&integral;}_0^{v_d}|h_2(t,0){|}^{2}tdt\&rsqb;---\left(9\right)$

Wherein, h₁(v, u) and h₂(v, u) is respectively the illumination end after adding Phase only pupil filters and the light at imaging end Pupil distribution function, v and u characterizes laterally and axially coordinate, v respectively_dFor pin hole radius.

Halfwidth can be obtained according to Rayleigh criterion and characterize resolution.

It is hereby achieved that after addition Phase only pupil filters, the halfwidth of psf is with the image of pin hole radius change.With As a example two ends all add phase filter, such as Fig. 3, after adding wave filter, the horizontal halfwidth of psf has a certain degree of subtracting Little, the change that the bigger wave filter of radius causes is bigger.

Result shows, when illumination end adds two area's phase filters, pin hole radius takes Airy disk size；Add at imaging end Enter wave filter or when two ends are simultaneously introduced wave filter, pin hole takes 1.5 times of Airy disks, and three kinds of situations all can make horizontal halfwidth be less than Simple microscope pin hole takes diffraction limit situation during Airy disk size, realizes super-resolution thus obtaining super resolution image.

In the picture, high fdrequency components correspond to the details of image, and the details of human eye is for prevention, diagnosis and the treatment of disease Suffer from very important effect, and pass through darkfield image and can obtain details in retina.

Pin hole is transformed, removes zeroth order bias light, you can to obtain darkfield image.

A kind of method is to translate the pin hole of Airy disk size, as shown in Figure 4.The now intensity of zeroth order light and translation distance Relational expression be:

$c\left(0\right)=2\frac{i_1\left(2\stackrel{\&overbar;}{v}\right)}{2\stackrel{\&overbar;}{v}}---\left(9\right)$

Wherein,For the translation distance of pin hole, j₁For first-order bessel function；

WhenWhen taking the radius that 3.83 are Airy disk, zeroth order light intensity is changed into for 0, can get darkfield image.

Another kind of method is to carry out central obscuration to confocal pinhole or wire is blocked, as shown in Figure 5.So can block Directly reflected light, has to Multiple Scattering light, thus obtaining darkfield image.

So an Airy disk distance is translated to Airy disk size pin hole, center is carried out to 1.5 times of Airy disk size pin holes Block or wire is blocked, you can realize dark-field imaging.

So can be achieved with the super-resolution confocal ophthalmoscope based on iris filter and dark field method.

Claims (5)

1. a kind of super-resolution confocal ophthalmoscope based on iris filter and dark field method it is characterised in that: include beacon light source (1), imaging source (2), illumination end iris filter (3), two-dimensional scanning mirrors (4), distorting lenss (5), the first optical filter (7), Hartmann sensor (8), the second optical filter (9), the first imaging end Phase only pupil filters (10), the first pin hole (11), the One photomultiplier tube (12), the second imaging end Phase only pupil filters (13), the second pin hole (14) and the second photomultiplier tube (15), wherein,

The light of beacon light source (1) reaches human eye (6) after two-dimensional scanning mirrors (4) and distorting lenss (5), passes through after reflection again Distorting lenss (5), two-dimensional scanning mirrors (4) and the first optical filter (7) reach Hartmann sensor (8), are calculated Wavefront Perturbation, Thus controlling distorting lenss (5) aberration correction；

The light of imaging source (2) reaches after illumination end iris filter (3), two-dimensional scanning mirrors (4) and distorting lenss (5) Human eye (6), through distorting lenss (5), two-dimensional scanning mirrors (4) and the second optical filter (9) after reflection, is further divided into two-beam, passes through First imaging end Phase only pupil filters (10) or the second imaging end Phase only pupil filters (13) and the first pin hole (11), after or the second pin hole (14), two width human eyes are obtained in the first photomultiplier tube (12) and the second photomultiplier tube (15) respectively Image, illuminates end filter distribution function h₁(v, u) represents, imaging end end filter distribution function all can use h₂(v, u) table Show, the point spread function on wherein any one road is all represented byCan lead to Cross point spread function to obtain horizontal halfwidth to characterize resolution, wherein, 1, only add illumination end iris filter in illumination end (3), when, the first pin hole (11) or the second pin hole (14) radius take Airy disk size；2nd, only add the first imaging end phase type pupil Wave filter (10) and the first pin hole (11) take 1.5 times of Airy disks or only add the second imaging end Phase only pupil filters (13) and Second pin hole (14) takes 1.5 times of Airy disks；3rd, after illumination end adds illumination end iris filter (3), add the first imaging end Phase only pupil filters (10) and the first pin hole (11) take 1.5 times of Airy disks or add the second imaging end phase type pupil Wave filter (13) and the second pin hole (14) take 1.5 times of Airy disks；Three kinds of situations all can make horizontal halfwidth be less than simple microscope Pin hole takes diffraction limit situation during Airy disk size, thus realizing super-resolution to obtain super resolution image, on this basis, to Chinese mugwort In speckle size pin hole translate an Airy disk distance, central obscuration is carried out to 1.5 times of Airy disk size pin holes or wire is blocked, Can achieve dark-field imaging.

2. the super-resolution confocal ophthalmoscope based on iris filter and dark field method according to required by claim 1, its feature It is: the first optical filter (7) only allows beacon light pass through, thus detecting human eye aberration；Second optical filter (9) only allows imaging light Pass through, thus obtaining human eye retina's image.

3. the super-resolution confocal ophthalmoscope based on iris filter and dark field method according to required by claim 1, its feature It is: beacon light source (1), human eye (6) and Hartmann sensor (8) composition independent optical paths, it is not subject to add iris filter and dark The impact of field technology, thus ensureing real-time detection and correcting human eye aberration, improves image resolution ratio and contrast.

4. the super-resolution confocal ophthalmoscope based on iris filter and dark field method according to required by claim 1, its feature It is: super-resolution effect and image intensity and illumination end iris filter (3) and the first imaging end Phase only pupil filters (10), the relative radius of the second imaging end Phase only pupil filters (13) are related, in the case that relative radius are less than 0.4, Radius bigger super-resolution effect is better, but image intensity is lower.

5. the super-resolution confocal ophthalmoscope based on iris filter and dark field method according to required by claim 1, its feature It is: the first imaging end Phase only pupil filters (10), the first pin hole (11), the first photomultiplier tube (12) and the second imaging End Phase only pupil filters (13), the second pin hole (14), the second photomultiplier tube (15) respectively constitute two sets of photodetection systems System is it is ensured that super resolution image and the darkfield image of retina can be obtained simultaneously.