CN116793988A - Near infrared deep tissue focusing system and method based on rapid mechanical calibration - Google Patents

Near infrared deep tissue focusing system and method based on rapid mechanical calibration Download PDF

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CN116793988A
CN116793988A CN202310608816.1A CN202310608816A CN116793988A CN 116793988 A CN116793988 A CN 116793988A CN 202310608816 A CN202310608816 A CN 202310608816A CN 116793988 A CN116793988 A CN 116793988A
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beam splitting
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unpolarized beam
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沈乐成
梁瀚朋
罗嘉伟
伍代轩
王戬
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Sun Yat Sen University
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Abstract

The invention discloses a near infrared deep tissue focusing system based on quick mechanical calibration, which comprises a control device, a laser, a pose adjusting device, a first unpolarized beam splitting cube, a second unpolarized beam splitting cube, a third unpolarized beam splitting cube, a first image sensor and a spatial light modulator, wherein the first image sensor and the spatial light modulator are respectively arranged at the symmetrical positions of the reflecting surfaces of the first unpolarized beam splitting cube, the second unpolarized beam splitting cube is arranged between the first unpolarized beam splitting cube and the spatial light modulator, and the third unpolarized beam splitting cube is arranged between the first unpolarized beam splitting cube and the first image sensor. The invention also discloses a near infrared deep tissue focusing method based on the rapid mechanical calibration. According to the invention, through the arrangement of the light paths and the arrangement of the pixel matching system and the focusing system, the symmetry degree of the light modulator and the image sensor is greatly improved, so that the focusing precision and speed of light passing through a scattering medium are improved.

Description

Near infrared deep tissue focusing system and method based on rapid mechanical calibration
Technical Field
The invention relates to the technical field of optical focusing of scattering media, in particular to a near infrared deep tissue focusing system and a near infrared deep tissue focusing method based on rapid mechanical calibration.
Background
Focusing light inside a scattering medium is a long sought-after goal in the optical field, and this technique has a wide range of applications in biomedical optics where depth of focus and accuracy are related to depth and resolution of imaging, i.e. to accuracy of medical diagnosis. Time-reversal ultrasound encoding (TRUE) focusing, combining the advantage of ultrasound relative transparency in biological tissue with efficient wavefront shaping based on Digital Optical Phase Conjugation (DOPC), has been proposed to address this problem. Iterative TRUE (itrate) focusing can further break the resolution barrier imposed by the acoustic diffraction limit by invoking repeated acousto-optic interactions, showing great potential for deep tissue biomedical applications.
In the prior art, there is an acousto-optic modulation phase conjugation method for realizing focusing inside a scattering medium, which comprises the following steps: phase extraction and phase conjugate reduction processes; in the phase extraction process, an object light path utilizes an acousto-optic modulation to construct a 'point light source' in a scattering medium, emergent speckles of the point light source interfere with modulated reference light generating corresponding frequency shift, the phase difference between the object light and the reference light is changed by adjusting the polarization state of the reference light, a phase conjugation system acquires a polarized phase shift interference pattern, and a four-step phase shift method is adopted to extract the light field phase; loading a phase conjugate graph of object light on the spatial light modulator during phase conjugate reduction, and generating time reversal light after direct irradiation of reference light so as to realize internal focusing of a scattering medium; the invention introduces an ultrasonic modulation signal on the basis of a polarization phase shift digital optical phase conjugation system, and can construct an acousto-optic action point in a scattering medium, thereby realizing optical focusing in the scattering medium by utilizing time reversal.
However, the focusing accuracy of the objective phase conjugation system and the itraue system based on the phase conjugation system is still limited by the symmetry degree of the optical modulator and the image sensor, which seriously affects the practical use of DOPC and itraue focusing.
Disclosure of Invention
The invention aims to overcome the defect that the system has strict requirements on the symmetry degree of a light modulator and an image sensor when an acousto-optic modulation phase conjugation method focuses in a scattering medium in the prior art so as to be difficult to practically use, and provides a near infrared deep tissue focusing system and a near infrared deep tissue focusing method based on quick mechanical calibration. According to the invention, through the arrangement of the light paths and the arrangement of the pixel matching system and the focusing system, the symmetry degree of the light modulator and the image sensor is greatly improved, so that the focusing precision and speed of light passing through a scattering medium are improved.
The aim of the invention can be achieved by adopting the following technical scheme:
the near infrared deep tissue focusing system based on the rapid mechanical calibration comprises a control device, a laser, a pose adjustment device, a first unpolarized beam splitting cube, a second unpolarized beam splitting cube, a third unpolarized beam splitting cube, a first image sensor and a spatial light modulator, wherein the first image sensor and the spatial light modulator are respectively arranged at the symmetrical positions of a reflecting surface of the first unpolarized beam splitting cube, the second unpolarized beam splitting cube is arranged between the first unpolarized beam splitting cube and the spatial light modulator, the third unpolarized beam splitting cube is arranged between the first unpolarized beam splitting cube and the first image sensor, an optical path adjustment structure is arranged between the laser and the first unpolarized beam splitting cube, the second unpolarized beam splitting cube and the third unpolarized beam splitting cube, so that laser beams are respectively led to the first unpolarized beam splitting cube, the second unpolarized beam splitting cube and the third unpolarized beam splitting cube, and the spatial light modulator are arranged on the pose adjustment device, and the laser pose adjustment device is connected with the first image sensor;
The system comprises a pair of first lenses, a pair of reflecting mirrors, a pair of second lenses, a pair of first lens and a pair of second reflecting mirrors, wherein the first reflecting mirrors and the first unpolarized beam splitting cube are respectively positioned at two ends of the optical axes of the pair of lenses, and the reflecting surface of the second reflecting mirror is aligned to one side of the second unpolarized beam splitting cube.
The focusing system comprises a second lens, a medium fixing structure, a fourth unpolarized beam splitting cube and a second image sensor, wherein the second lens, the medium fixing structure, the fourth unpolarized beam splitting cube and the second image sensor are arranged between the first unpolarized beam splitting cube and the light path adjusting structure in sequence, the light path adjusting structure is located on the other side of the fourth unpolarized beam splitting cube relative to the medium fixing structure, and the second image sensor and the medium fixing structure are located on the symmetrical positions of the reflecting surfaces of the fourth unpolarized beam splitting cube respectively.
The phase conjugation system has a large number of devices, the pose of each device needs higher precision, the two devices are contradictory to a common optical system, and various devices have uncontrollable aberration. The basic principle of phase conjugation is to make the propagation of electromagnetic wave achieve the effect similar to time inversion by utilizing the time symmetry of wave equation on wave function solution. In a Digital Optical Phase Conjugation (DOPC) system consisting of an image sensor and a Spatial Light Modulator (SLM), the image sensor and the SLM are positioned at symmetrical positions of a reflecting surface of a non-polarized beam splitting cube (BS), a control device such as a computer calculates complex amplitude distribution (or phase diagram) of speckle interference patterns recorded by the image sensor through four-step phase shift holography, conjugates the complex amplitude distribution (or phase diagram) and loads the processed phase diagram on the SLM immediately, so that the reverse propagation of light waves and focusing through a scattering medium are realized. However, since the SLM and the image sensor of the DOPC system are on opposite sides of the BS and are not visible to each other, the first difficulty to be solved in the calibration is the pixel matching of the image sensor and the SLM.
Therefore, in order to match the pixels of the image sensor and the SLM, the SLM is adjusted by the pose adjusting means so that the bright-dark meshes formed after the pixel points of the first image sensor interfere with the SLM are matched with each other. In the process, the invention adds a pixel matching system, wherein a pair of first lenses are optical 4f systems, so that the SLM and the first image sensor are positioned on the front focal plane of the first lens, the first reflector is positioned on the back focal plane of the second first lens, and the 4f system has the advantages that even if the first lens has a certain offset in the plane, the secondary imaging can correct a small range of displacement errors due to the reversible principle of the light path, and the pitching and the tilting angles of the reflectors have only the effect of the angle of the image rather than the position of the lens imaging system, thereby greatly improving the fault tolerance rate of the light path adjustment, so that the SLM can be perfectly imaged on the first image sensor to realize better pixel matching. While a second mirror is provided to reflect reference light that has not passed through the SLM back into the optical path to interfere with the reflected light of the spatial modulator.
After the pixel matching is completed, the scattering medium is placed in the medium-fixed structure, at which time the second image sensor can only get a very blurred focus, because the pixel matching cannot calibrate the pitch and tilt angle of the SLM to an optimal pose. Therefore, the pose adjusting device is used for adjusting six degrees of freedom of the SLM one by one, simultaneously recording the intensity of the focus in the second image sensor, and recording absolute coordinates of the electric displacement table and the rotary table when the highest peak intensity is reached, so that the optimal pose of the SLM can be obtained. The pose adjusting device can be a six-axis motor or other devices capable of adjusting SML six degrees of freedom, and because only a simple serial port command is sent to the motor without huge complex amplitude and matrix operation, the whole mechanical calibration process generally only takes 10 minutes, self-adaptive stepping precision scanning controlled by PID (proportion integration differentiation) can be added, the mechanical calibration can be even shortened to 3-5 minutes, and the time consumed by other DOPC systems in the world in pure digital six-axis pose compensation is far less.
Through the above-described coarse adjustment of the pixel matching and fine adjustment of the six degrees of freedom of the SLM, a very sharp focus already appears on the second image sensor.
Further, the device also comprises an ultrasonic focusing system, wherein the ultrasonic focusing system comprises an ultrasonic transducer and a light blocking structure, the ultrasonic transducer is arranged between the medium fixing structure and the fourth unpolarized beam splitting cube, and the light blocking structure can enable the fourth unpolarized beam splitting cube and the light path adjusting structure to be in a state of allowing light to pass or blocking light to pass.
The frequency of use is f US The self-focusing ultrasonic transducer of the (2) emits ultrasonic beams to the inside of the scattering medium, the focus of the ultrasonic beams emitted by the ultrasonic transducer is positioned between the fourth unpolarized beam splitting cube and the scattering medium, when the light which is firstly incident passes through the ultrasonic focus, the frequency shift is generated by partial reflected light due to stronger acousto-optic effect, and the partial light is similar to the frequency of the reference light, so that the detection can be performed through heterodyne interference. The phase conjugation system then inverts only the reflected light passing through the ultrasound focus, so that the reflected light is focused inside the scattering medium. At the same time, the DOPC system is also easily combined with various guiding targets, further enabling focusing inside the scattering medium. In biological tissue, ultrasonic waves have excellent penetrability due to their large wavelength, compared to the strong scattering property of light, and thus can be used as a guiding target with excellent performance.
Further, the ultrasonic focusing system further comprises a transparent water tank, the fourth unpolarized beam splitting cubes are respectively designed in the transparent water tank, the focus of the ultrasonic transducer is positioned in the transparent water tank, and a semi-transparent reflector is arranged between the focus of the ultrasonic transducer and the fourth unpolarized beam splitting cubes.
Because of the high impedance of air to ultrasound, the ultrasound transducer should be immersed in water in order to conduct ultrasound better. To facilitate the observation of the focusing situation, the TRUE system typically does not use a bulk scattering medium, but rather a sandwich structure (scattering medium-water-scattering medium) that allows light to travel through a distance of free space. The conventional iTRUE system adds a fluorescent film at the position of focusing the light beam so as to shoot the scattering medium at the side by using a camera, the implementation difficulty of the mode in the invisible light band is huge, the energy utilization efficiency is extremely low, only the sectional view of the light beam can be observed, and the two-dimensional distribution of the front face of the focus cannot be intuitively reflected. According to the invention, one scattering medium is replaced by the half-mirror, so that the frequency-shift light energy is returned to be received by the second image sensor, and the focus can be observed well.
Further, the light path adjusting structure comprises a reflecting mirror, a half-wave plate and a first beam expanding structure, wherein the reflecting mirror is used for enabling laser emitted by the laser to enter the second unpolarized beam splitting cube, the half-wave plate is positioned on a laser light path, and the first beam expanding structure is positioned between the half-wave plate and the second unpolarized beam splitting cube;
The light path adjusting structure further comprises a fifth unpolarized beam splitting cube for splitting laser emitted by the laser, an acousto-optic modulator (AOM) and a second beam expanding structure which are sequentially arranged in the direction of reflected light of the fifth unpolarized beam splitting cube, and an acousto-optic modulator arranged between the third unpolarized beam splitting cube and the half-wave plate, wherein half-wave plates are arranged in the incident direction and the reflecting direction of the fifth unpolarized beam splitting cube.
The light path adjusting structure further comprises a sixth unpolarized beam splitting cube for splitting laser emitted by the laser, an acousto-optic modulator arranged between the fourth unpolarized beam splitting cube and the sixth unpolarized beam splitting cube, and an acousto-optic modulator arranged between the sixth unpolarized beam splitting cube and the half-wave plate, and half-wave plates are arranged on the incidence direction and the reflection direction of the sixth unpolarized beam splitting cube.
According to the scheme, the light path is directly arranged through the structure, and the positions and the number of the reflecting mirrors and the unpolarized beam splitting cubes can be changed as required, so that light rays emitted by the laser can enter the first unpolarized beam splitting cube, the second unpolarized beam splitting cube and the third unpolarized beam splitting cube respectively. The first beam expanding structure and the second beam expanding structure can be beam expanding structures formed by two lenses, or other structures capable of changing the size of the light beam do not affect the implementation of the scheme.
Further, the laser is a near infrared light generator.
Deep biological tissue focusing and imaging suffers from the long-term difficulty that photons are absorbed in large amounts by various particles and scattered too strongly to go to application. Wave front shaping technology can only overcome the scattering of light by a scattering medium, cannot eliminate the influence of absorption, and most biological tissues absorb visible light more strongly, so that unnecessary energy loss is caused. In addition, while the phase conjugation system has powerful performance, it is limited by the size of the Spatial Light Modulator (SLM), which still belongs to part of the spatial modulation system, meaning that it cannot modulate scattered light outside the spillover optical path. Since near infrared light has a longer wavelength than visible light, and its magnitude is comparable to the size of various scatterers in living beings, infrared light is weaker in Mie scattering when passing through, and can penetrate deeper tissues. Meanwhile, due to the excellent property of near infrared light, thicker muscle tissues and thinner bones can be penetrated, and the technology is expected to be applied to subcutaneous laser treatment, noninvasive high-resolution brain microscopic imaging and optogenetic research. But in the invisible light wave band, the optical path construction and error control of the phase conjugation system are particularly difficult, and the focusing system provided by the invention has the advantages of rapid calibration and high focusing precision, so that the availability of realizing the focusing of light penetrating through a scattering medium by utilizing an infrared light source is higher.
A near infrared deep tissue focusing method based on rapid mechanical calibration comprises the following steps:
s1: the reference light formed by the light emitted by the laser after passing through the light path adjusting structure causes the reference light to interfere with the reflected light of the spatial light modulator, so that the image generated by the spatial light modulator has a specific interference pattern;
the reference light formed by an acousto-optic modulator (AOM) enters a third unpolarized beam splitting cube, and the laser enters the second unpolarized beam splitting cube through an optical path adjusting structure and then enters a Spatial Light Modulator (SLM) to form reflected light of the spatial light modulator.
S2: adjusting the pose adjustment device to adjust Δx, Δy, Δz, and Δθ for the spatial light modulator z Coarse adjustment is performed in four degrees of freedom, so that the first image sensor senses an image generated by the spatial light modulator and the image generated by the spatial light modulator corresponds to each pixel of the first image sensor;
s3: placing a scattering medium in the medium fixing structure, enabling the reference light and the sample light passing through the scattering medium to form heterodyne interference, continuously recording a plurality of frames of interferograms recognized by the first image sensor by the control device, calculating a phase diagram, loading the calculated phase diagram on the spatial light modulator to enable light beams to reversely penetrate the scattering medium, reforming parallel light beams entering the sample, and focusing the parallel light beams on the second image sensor;
The laser enters the scattering medium after entering the fourth unpolarized beam splitting cube through the light path adjusting structure to form sample light passing through the scattering medium, the sample light enters from one side of the scattering medium, and the reformed parallel light beam entering the sample re-enters the scattering medium from the other side of the scattering medium. The first sensor records at least 2 frames of interferograms.
S4: the control device controls the pose adjusting device to adjust the delta x, delta y, delta z and delta theta of the spatial light modulator x 、Δθ y 、Δθ z The six degrees of freedom are regulated one by one, and the control device records the peak intensity of the focus in the image identified by the second image sensor and the coordinate position and angle of the corresponding spatial light modulator, so as to obtain the optimal pose of the spatial light modulator.
Further, in the step S3, the method further includes the following steps:
adjusting the frequency of an acousto-optic modulator (AOM) to f US And the beat frequency f of the two M At 10Hz, heterodyne interference is formed between the sample light and the reference light generated by AOM, the first image sensor is a scientific grade CMOS camera (sCMOS), the second image sensor is an industrial grade CMOS camera, and the sCMOS frame rate is set to 4f M After continuously recording 4 frames of interferograms, loading the conjugate of the calculated phase diagram in the space light modulation The beam is made to pass back through the scattering medium on the actuator, reformed into a parallel beam that is incident on the sample, and focused on the CMOS.
Further, the method also comprises the following steps:
s5: and (3) taking a multi-order Zernike polynomial, scanning each order of coefficients in the order from low order to high order, feeding back the focus peak intensity of the second image sensor to obtain the optimal coefficients of each order, and superposing a final Zernike compensation phase diagram on the conjugate phase diagram in the step (S3).
After step S4, a very sharp focus has been present on the second image sensor, but there is still a gap in the performance from the limit of the DOPC system. One of the reasons is that the surface curvature of the SLM is not ideal, and today the wafer fabrication process still has certain drawbacks, and there is a high probability that there will be a certain curvature of the back plate of a single LCoS (liquid crystal on silicon) die. Although this variation typically has a height difference from center to edge of less than 10 μm, it has little effect on the geometrical optical imaging system, but it can degrade the modulated wavefront in phase-modulation based DOPC systems. Secondly, limited by the level of technology of the various optical elements in the optical path, such as insufficient flatness of the mirrors and incomplete correction of higher order aberrations of the lenses, slight wave aberrations inevitably occur for all beams. These imperfections are completely independent of the pose of the SLM and can only be digitally compensated by loading the corresponding phase map through the SLM.
For a general DOPC device, the SLM at the tail end of the system plays roles of light field regulation and error compensation, namely, in the system debugging stage, phase distortion generated by accumulation of the system is calculated according to a certain feedback algorithm, the phase diagram is preloaded on the SLM, and then phase conjugation is carried out on scattered light wave fronts generated by a sample to realize high-quality focusing through a scattering medium. The early calculation of the digital compensation mode consumes a great deal of time, has limited precision and small adjustment range, and cannot compensate for larger errors in the invisible light system.
The invention therefore performs digital compensation on the basis of the mechanical calibration of the focusing system. The method is characterized by Zernike polynomials, almost any phase diagram can be generated by linear superposition of the polynomials, and the solution of the coefficients of each order of the Zernike polynomials is similar to the 6-degree-of-freedom correction of the pose of the SLM, so that the method obtains a sharper focus by carrying out digital compensation on the Zernike polynomials. In the invention, the step S4 carries out fine adjustment by adjusting the displacement of the SLM, and the mechanical calibration is carried out quickly, and then the step S5 carries out digital compensation to further improve the calibration precision.
Further, in the step S5, an 8 th order zernike polynomial is taken; the scanning range of each order coefficient is [ -2,2], and the stepping precision is 0.01.
The phase diagram multiplies different coefficients, detects the change of the brightness of the focus in real time, and records the coefficient corresponding to the strongest focus. When 1-3 steps of scanning are performed, focusing accuracy is obviously improved, but the higher the Zernike aberration is, the larger the change of the shape is, and the scanning time is increased. In the scheme, an 8-order Zernike polynomial is taken.
Further, the method also comprises the following steps:
s6: the ultrasonic transducer emits ultrasonic beams into the scattering medium, the incident light of the scattering medium passes through an ultrasonic intersection point to enable partial reflected light to shift in frequency, then heterodyne interference is carried out on the reference light generated by the laser and the partial reflected light to detect the partial reflected light, and finally the control device inverts the reflected light passing through an ultrasonic focus point to focus on the inside of the scattering medium.
Further, the method also comprises the following steps:
s7: performing multiple iterations on the inverted light as incident light of a scattering medium;
in step S6, a regular focused beam is first incident into the medium, and then a weak signal light (marking light) is reflected from the place passing through the ultrasonic focus, and the reflected light is inverted by phase conjugation. At this time, the full width at half maximum of the first formed focus is observed to be close to the full width at half maximum of the ultrasound Jiao Dianban, and the quality of the focus in the medium after inversion is poor due to the low signal-to-noise ratio of the first reflected light, but the light near the ultrasound focus is increased this time, so that the signal-to-noise ratio is enhanced when the reflected light is reflected again, and the reflected marking light is conjugated continuously, so that the marking light is focused in the scattering medium. These steps are repeated continuously, and the focus in the medium becomes stronger and smaller.
Compared with the prior art, the invention has the beneficial effects that:
(1) The first image sensor and the spatial light modulator are arranged at the symmetrical positions of the reflecting surface of the first unpolarized beam splitting cube, and the second unpolarized beam splitting cube and the pixel matching system are arranged to realize the pixel matching of the image generated by the spatial light modulator and the first image sensor, and then the focusing system is used for focusing rapidly, so that the high-quality focusing of light passing through the scattering medium is realized.
(2) Based on mechanical calibration, digital compensation is performed based on a Zernike polynomial, so that the accuracy of a focus is further improved and the calibration time is reduced.
(3) The wave-front shaping technology is widened to invisible light wave band and better performance is obtained, so that one step of wave-front shaping is promoted on deep tissue biological imaging, and a certain technical support is provided for other long-distance self-adaptive optical imaging
Drawings
FIG. 1 is a schematic diagram of a DOPC focusing system of the present invention;
FIG. 2 is a schematic diagram of an iTRUE focusing system according to the present invention;
FIG. 3 is a flow chart of the method of the present invention;
FIG. 4 is a schematic view of the elevation of the brightness of a focus through a scattering medium during mechanical calibration of an SLM of the present invention;
FIG. 5 is a schematic diagram of the focusing effect of the present invention through a scattering medium during system calibration;
fig. 6 is a schematic diagram of the present invention for focusing and iterating a focal spot inside a scattering medium.
The graphic indicia are illustrated as follows:
1-laser, 2-pose adjustment device, 31-first unpolarized beam splitting cube, 32-second unpolarized beam splitting cube, 33-third unpolarized beam splitting cube, 4-first image sensor, 5-spatial light modulator, 6-pixel matching system, 61-first lens, 62-first mirror, 63-second mirror, 7-focusing system, 71-second lens, 72-fourth unpolarized beam splitting cube, 73-second image sensor, 8-ultrasonic focusing system, 81-ultrasonic transducer, 82-light blocking structure, 83-transparent water tank, 84-semi-transparent mirror, 9-optical path adjustment structure, 91-mirror, 92-half wave plate, 93-first beam expanding structure, 94-fifth unpolarized beam splitting cube, 95-acoustic light modulator, 96-second beam expanding structure, 97-sixth unpolarized beam splitting cube.
Detailed Description
The invention is further described below in connection with the following detailed description. Wherein the drawings are for illustrative purposes only and are shown in schematic, non-physical, and not intended to be limiting of the present patent; for the purpose of better illustrating embodiments of the invention, certain elements of the drawings may be omitted, enlarged or reduced and do not represent the size of the actual product; it will be appreciated by those skilled in the art that certain well-known structures in the drawings and descriptions thereof may be omitted.
The same or similar reference numbers in the drawings of embodiments of the invention correspond to the same or similar components; in the description of the present invention, it should be understood that, if there is an azimuth or positional relationship indicated by terms such as "upper", "lower", "left", "right", etc., based on the azimuth or positional relationship shown in the drawings, it is only for convenience of describing the present invention and simplifying the description, but it is not indicated or implied that the apparatus or element referred to must have a specific azimuth, be constructed and operated in a specific azimuth, and thus terms describing the positional relationship in the drawings are merely illustrative and should not be construed as limitations of the present patent, and specific meanings of the terms described above may be understood by those skilled in the art according to specific circumstances.
Example 1
As shown in fig. 1 and fig. 2, a near infrared deep tissue focusing system based on rapid mechanical calibration comprises a control device, a laser 1, a pose adjustment device 2, a first unpolarized beam splitting cube 31, a second unpolarized beam splitting cube 32, a third unpolarized beam splitting cube 33, a first image sensor 4 and a spatial light modulator 5, wherein the first image sensor 4 and the spatial light modulator 5 are respectively arranged at the symmetrical positions of the reflecting surfaces of the first unpolarized beam splitting cube 31, the second unpolarized beam splitting cube 32 is arranged between the first unpolarized beam splitting cube 31 and the spatial light modulator 5, the third unpolarized beam splitting cube 33 is arranged between the first unpolarized beam splitting cube 31 and the first image sensor 4, an adjustment structure 9 is arranged between the laser 1 and the first unpolarized beam splitting cube 31, the second unpolarized beam splitting cube 32 and the third unpolarized beam splitting cube 33 so that laser beams are respectively led to the first unpolarized beam splitting cube 31, the second unpolarized beam splitting cube 32 and the third unpolarized beam splitting cube 5, and the pose adjustment device 4 are respectively arranged on the pose adjustment device 2 and the laser device 2;
The pixel matching system 6 is further included, the pixel matching system 6 comprises a pair of first lenses 61 and a pair of reflecting mirrors 91, the reflecting mirrors 91 comprise a first reflecting mirror 62 and a second reflecting mirror 63, the first reflecting mirror 62 and the first unpolarized beam splitting cube 31 are respectively positioned at two ends of the optical axes of the pair of lenses, and the reflecting surface of the second reflecting mirror 63 is aligned with one side of the second unpolarized beam splitting cube 32.
The focusing system 7 is arranged between the first unpolarized beam splitting cube 31 and the light path adjusting structure 9, the focusing system 7 comprises a second lens 71, a medium fixing structure, a fourth unpolarized beam splitting cube 72 and a second image sensor 73 which are arranged between the first unpolarized beam splitting cube 31 and the light path adjusting structure 9, the second lens 71, the medium fixing structure and the fourth unpolarized beam splitting cube 72 are sequentially arranged, the light path adjusting structure 9 is positioned on the other side of the fourth unpolarized beam splitting cube 72 relative to the medium fixing structure, and the second image sensor 73 and the medium fixing structure are respectively positioned on the reflecting surface symmetrical positions of the fourth unpolarized beam splitting cube 72.
The phase conjugation system has a large number of devices, the pose of each device needs higher precision, the two devices are contradictory to a common optical system, and various devices have uncontrollable aberration. The basic principle of phase conjugation is to make the propagation of electromagnetic wave achieve the effect similar to time inversion by utilizing the time symmetry of wave equation on wave function solution. In a Digital Optical Phase Conjugation (DOPC) system consisting of an image sensor and a spatial light modulator 5 (SLM), the image sensor and the SLM are positioned at symmetrical positions of a reflecting surface of a non-polarized beam splitting cube (BS), a control device such as a computer calculates complex amplitude distribution (or phase diagram) of speckle interference patterns recorded by the image sensor through four-step phase shift holography, conjugates the complex amplitude distribution (or phase diagram) and loads the processed phase diagram on the SLM immediately, so that the reverse propagation of light waves and focusing through a scattering medium are realized. However, since the SLM and the image sensor of the DOPC system are on opposite sides of the BS and are not visible to each other, the first difficulty to be solved in the calibration is the pixel matching of the image sensor and the SLM.
Therefore, in order to match the pixels of the image sensor and the SLM, the SLM is adjusted by the pose adjustment device 2 so that the bright-dark grid formed after the pixel points of the first image sensor 4 interfere with the SLM matches each other. In this process, the present invention adds a pixel matching system 6, wherein a pair of first lenses 61 are optical 4f systems, so that the SLM and the first image sensor 4 are both located on the front focal plane of the first lens 61, and the first mirror 62 is located on the back focal plane of the second first lens 61, and the 4f system has the advantage that even if the first lens 61 has a certain offset in its plane, the secondary imaging can correct a small range of displacement errors due to the principle of reversible optical path, and the influence of the pitch and tilt angles of the mirror 91 on the lens imaging system is only the angle of the image and not the position, so that the fault tolerance of the optical path adjustment is greatly improved, and the SLM can be perfectly imaged on the first image sensor 4 to achieve better pixel matching. While a second mirror 63 is provided to reflect reference light that has not passed through the SLM back into the optical path so as to interfere with the reflected light of the spatial modulator.
After the pixel matching is completed, the scattering medium is placed in the medium-fixed structure, at which time the second image sensor 73 can only get a very blurred focus, because the pixel matching does not calibrate the pitch and tilt angle of the SLM to an optimal pose. Therefore, the pose adjusting device 2 is used to adjust six degrees of freedom of the SLM one by one, and record the intensity of the focal point in the second image sensor 73, and the absolute coordinates of the electric displacement table and the rotating table when the highest peak intensity is reached are recorded, so that the optimal pose of the SLM can be obtained. The pose adjusting device 2 can be a six-axis motor or other devices capable of adjusting SML six degrees of freedom, and because only a simple serial port command is sent to the motor without huge complex amplitude and matrix operation, the whole mechanical calibration process generally only takes 10 minutes, self-adaptive stepping precision scanning controlled by PID can be added, the mechanical calibration can be shortened to 3-5 minutes, and the time consumed by other DOPC systems in the world in pure digital six-axis pose compensation is far less.
Through the above-described coarse adjustment of the pixel matching and fine adjustment of the six degrees of freedom of the SLM, a very sharp focus already appears on the second image sensor 73.
The ultrasonic focusing system 8 is further included, the ultrasonic focusing system 8 comprises an ultrasonic transducer 81 and a light blocking structure 82, the ultrasonic transducer 81 is arranged between the medium fixing structure and the fourth unpolarized beam splitting cube 72, and the light blocking structure 82 can enable light to pass through or block light to pass through between the fourth unpolarized beam splitting cube 72 and the light path adjusting structure 9.
The frequency of use is f US The self-focusing ultrasonic transducer 81 of the above-mentioned device emits an ultrasonic beam to the inside of the scattering medium, the focal point of the ultrasonic beam emitted by the ultrasonic transducer 81 is located between the fourth unpolarized beam splitting cube 72 and the scattering medium, when the light which is incident for the first time passes through the ultrasonic focal point, the frequency shift is generated due to the stronger acousto-optic effect of the partial reflected light, and the partial light is similar to the frequency of the reference light, so that the detection can be performed through heterodyne interference. The phase conjugation system then inverts only the reflected light passing through the ultrasound focus, so that the reflected light is focused inside the scattering medium. At the same time, the DOPC system is also easily combined with various guiding targets, further enabling focusing inside the scattering medium. In biological tissue, ultrasonic waves have excellent penetrability due to their large wavelength, compared to the strong scattering property of light, and thus can be used as a guiding target with excellent performance.
The ultrasonic focusing system 8 further comprises a transparent water tank 83, the fourth unpolarized beam splitting cube 72 is designed in the transparent water tank 83, the focus of the ultrasonic transducer 81 is positioned in the transparent water tank 83, and a semi-transparent reflector 84 is arranged between the focus of the ultrasonic transducer 81 and the fourth unpolarized beam splitting cube 72.
Because of the high impedance of air to ultrasound, the ultrasound transducer 81 should be immersed in water in order to conduct ultrasound better. To facilitate the observation of the focusing situation, the TRUE system typically does not use a bulk scattering medium, but rather a sandwich structure (scattering medium-water-scattering medium) that allows light to travel through a distance of free space. The conventional iTRUE system adds a fluorescent film at the position of focusing the light beam so as to shoot the scattering medium at the side by using a camera, the implementation difficulty of the mode in the invisible light band is huge, the energy utilization efficiency is extremely low, only the sectional view of the light beam can be observed, and the two-dimensional distribution of the front face of the focus cannot be intuitively reflected. The invention replaces one of the scattering media with a half mirror, which allows the frequency-shifted light energy to be received back by the second image sensor 73 and also allows the focus to be well observed.
The light path adjusting structure 9 comprises a reflecting mirror 91 for enabling laser light emitted by the laser 1 to enter the second unpolarized beam splitting cube 32, a half-wave plate 92 positioned on the light path of the laser light, and a first beam expanding structure 93 positioned between the half-wave plate 92 and the second unpolarized beam splitting cube 32;
The optical path adjusting structure 9 further includes a fifth unpolarized beam splitting cube 94 for splitting the laser light emitted from the laser 1, an acousto-optic modulator 95 (AOM) and a second beam expanding structure 96 which are sequentially disposed in the direction of the reflected light of the fifth unpolarized beam splitting cube, and an acousto-optic modulator 95 disposed between the third unpolarized beam splitting cube 33 and the half-wave plate 92, and half-wave plates 92 are disposed in the incident and reflection directions of the fifth unpolarized beam splitting cube 94.
The optical path adjusting structure 9 further includes a sixth unpolarized beam splitting cube 97 for splitting the laser light emitted from the laser 1, an acousto-optic modulator 95 disposed between the fourth unpolarized beam splitting cube 72 and the sixth unpolarized beam splitting cube 97, and an acousto-optic modulator 95 disposed between the sixth unpolarized beam splitting cube 97 and the half-wave plate 92, and the half-wave plate 92 is disposed in both the incident and reflection directions of the sixth unpolarized beam splitting cube 97.
The optical path is directly arranged through the above-mentioned simple structure, and the positions and the number of the reflecting mirror 91 and the unpolarized beam splitting cube can be changed as required, so that the light rays emitted by the laser 1 can respectively enter the first unpolarized beam splitting cube 31, the second unpolarized beam splitting cube 32 and the third unpolarized beam splitting cube 33. The first beam expanding structure 93 and the second beam expanding structure 96 may be beam expanding structures formed by two lenses, or other structures capable of changing the size of the light beam, which do not affect the implementation of the present solution.
The laser 1 is a near infrared light generator.
Deep biological tissue focusing and imaging suffers from the long-term difficulty that photons are absorbed in large amounts by various particles and scattered too strongly to go to application. Wave front shaping technology can only overcome the scattering of light by a scattering medium, cannot eliminate the influence of absorption, and most biological tissues absorb visible light more strongly, so that unnecessary energy loss is caused. In addition, while the phase conjugation system has powerful performance, it is limited by the size of the spatial light modulator 5 (SLM), which still belongs to part of the spatial modulation system, meaning that it cannot modulate scattered light outside the spillover optical path. Since near infrared light has a longer wavelength than visible light, and its magnitude is comparable to the size of various scatterers in living beings, infrared light is weaker in Mie scattering when passing through, and can penetrate deeper tissues. Meanwhile, due to the excellent property of near infrared light, thicker muscle tissues and thinner bones can be penetrated, and the technology is expected to be applied to subcutaneous laser treatment, noninvasive high-resolution brain microscopic imaging and optogenetic research. But in the invisible light wave band, the optical path construction and error control of the phase conjugation system are particularly difficult, and the focusing system provided by the invention has the advantages of rapid calibration and high focusing precision, so that the availability of realizing the focusing of light penetrating through a scattering medium by utilizing an infrared light source is higher.
Example 2
As shown in fig. 1 to 3, a near infrared deep tissue focusing method based on rapid mechanical calibration includes the following steps:
s1: the reference light formed by the light emitted by the laser 1 after passing through the light path adjusting structure 9 causes the reference light to interfere with the reflected light of the spatial light modulator 5, so that the image generated by the spatial light modulator 5 has a specific interference pattern;
the reference light formed by the acousto-optic modulator 95 (AOM) enters the third unpolarized beam splitting cube 33, and the laser 1 enters the second unpolarized beam splitting cube 32 through the optical path adjusting structure 9 and then enters the spatial light modulator 5 (SLM) to form the reflected light of the spatial light modulator 5.
S2: the pose adjustment device 2 is adjusted so as to be deltax, deltay, deltaz, and deltatheta of the spatial light modulator 5 z Coarse-tuning is performed in four degrees of freedom, so that the first image sensor 4 senses an image generated by the spatial light modulator 5, and the image generated by the spatial light modulator 5 corresponds to each pixel of the first image sensor 4;
s3: placing a scattering medium in the medium fixing structure so that the reference light forms heterodyne interference with the sample light passing through the scattering medium, continuously recording a plurality of frames of interferograms recognized by the first image sensor 4 by the control device, calculating a phase diagram, loading the calculated phase diagram on the spatial light modulator 5 to enable light beams to reversely penetrate the scattering medium, reforming parallel light beams which are injected into the sample, and focusing on the second image sensor 73;
The laser 1 enters the scattering medium after entering the fourth unpolarized beam splitting cube through the light path adjusting structure to form sample light passing through the scattering medium, the sample light enters from one side of the scattering medium, and the reformed parallel light beam entering the sample re-enters the scattering medium from the other side of the scattering medium. The first sensor records at least 2 frames of interferograms.
S4: the control device controls the pose adjustment device 2 to control Δx, Δy, Δz, Δθ of the spatial light modulator 5 x 、Δθ y 、Δθ z The six degrees of freedom are regulated one by one, and the control device records the peak intensity of the focus in the image identified by the second image sensor 73 and the corresponding coordinate position and angle of the spatial light modulator 5, so as to obtain the optimal pose of the spatial light modulator 5.
In step S3, the method further includes the following steps:
adjusting the frequency of an acousto-optic modulator 95 (AOM) to f US And the beat frequency f of the two M At 10Hz, the sample light forms heterodyne interference with the reference light generated by the AOM, the first image sensor 4 is a scientific grade CMOS camera (sCMOS), the second image sensor 73 is an industrial grade CMOS camera, and the sCMOS frame rate is set to 4f M After continuously recording 4 frames of interferograms, the conjugate of the calculated phase diagram is loaded on the spatial light modulator 5 to enable the light beam to reversely penetrate through the scattering medium, and a parallel light beam which is injected into the sample is formed again and focused on the CMOS.
The method also comprises the following steps:
s5: taking a multi-order Zernike polynomial, scanning each order coefficient in the order from low order to high order, feeding back the focus peak intensity of the second image sensor 73 to obtain each order optimal coefficient, and superposing a final Zernike compensation phase diagram on the conjugate phase diagram in the step S3.
After step S4, a very sharp focus has been present on the second image sensor 73, but there is still a gap in the performance from the limit of the DOPC system. One of the reasons is that the surface curvature of the SLM is not ideal, and today the wafer fabrication process still has certain drawbacks, and there is a high probability that there will be a certain curvature of the back plate of a single LCoS (liquid crystal on silicon) die. Although this variation typically has a height difference from center to edge of less than 10 μm, it has little effect on the geometrical optical imaging system, but it can degrade the modulated wavefront in phase-modulation based DOPC systems. Secondly, limited by the level of technology of the various optical elements in the optical path, such as insufficient flatness of the mirror 91 and incomplete correction of higher order aberrations of the lens, slight wave aberration of all the beams inevitably occurs. These imperfections are completely independent of the pose of the SLM and can only be digitally compensated by loading the corresponding phase map through the SLM.
For a general DOPC device, the SLM at the tail end of the system plays roles of light field regulation and error compensation, namely, in the system debugging stage, phase distortion generated by accumulation of the system is calculated according to a certain feedback algorithm, the phase diagram is preloaded on the SLM, and then phase conjugation is carried out on scattered light wave fronts generated by a sample to realize high-quality focusing through a scattering medium. The early calculation of the digital compensation mode consumes a great deal of time, has limited precision and small adjustment range, and cannot compensate for larger errors in the invisible light system.
The invention thus performs digital compensation on the basis of the mechanical calibration of the focusing system 7. The method is characterized by Zernike polynomials, almost any phase diagram can be generated by linear superposition of the polynomials, and the solution of the coefficients of each order of the Zernike polynomials is similar to the 6-degree-of-freedom correction of the pose of the SLM, so that the method obtains a sharper focus by carrying out digital compensation on the Zernike polynomials. In the invention, the step S4 carries out fine adjustment by adjusting the displacement of the SLM, and the mechanical calibration is carried out quickly, and then the step S5 carries out digital compensation to further improve the calibration precision.
In the step S5, 8-order Zernike polynomials are taken; the scanning range of each order coefficient is [ -2,2], and the stepping precision is 0.01.
The phase diagram multiplies the coefficients of different Zernike phases, detects the change of the brightness of the focus in real time, and records the coefficient corresponding to the strongest focus. When 1-3 steps of scanning are performed, focusing accuracy is obviously improved, but the higher the Zernike aberration is, the larger the change of the shape is, and the scanning time is increased. In the scheme, an 8-order Zernike polynomial is taken.
The method also comprises the following steps:
s6: the ultrasonic transducer 81 emits an ultrasonic beam into the scattering medium, and makes the incident light of the scattering medium pass through an ultrasonic intersection point to shift the frequency of a part of reflected light, then heterodyne interference is carried out on the reference light generated by the laser 1 and the part of reflected light to detect the part of reflected light, and finally the control device inverts the reflected light passing through an ultrasonic focus, so that the light can be focused into the scattering medium.
The method also comprises the following steps:
s7: performing multiple iterations on the inverted light as incident light of a scattering medium;
in step S6, a regular focused beam is first incident into the medium, and then a weak signal light (marking light) is reflected from the place passing through the ultrasonic focus, and the reflected light is inverted by phase conjugation. At this time, the full width at half maximum of the first formed focus is observed to be close to the full width at half maximum of the ultrasound Jiao Dianban, and the quality of the focus in the medium after inversion is poor due to the low signal-to-noise ratio of the first reflected light, but the light near the ultrasound focus is increased this time, so that the signal-to-noise ratio is enhanced when the reflected light is reflected again, and the reflected marking light is conjugated continuously, so that the marking light is focused in the scattering medium. These steps are repeated continuously, and the focus in the medium becomes stronger and smaller.
In this embodiment, after 5 iterations, the focused light energy is rapidly folded to form a sharp focus, the full width at half maximum of which is about 1/6 of the ultrasonic focus, very close to the theoretical limit.
Example 3
One of the important indicators measuring the focusing performance of a wavefront shaping system is the PBR (peak-to-background ratio), i.e. the ratio of the peak intensity of the focal spot to the average intensity of the speckle background outside the full width at half maximum.
FIG. 4 is a schematic view showing the elevation of the brightness of a focus through a scattering medium during mechanical calibration of the SLM of the present invention.
The enhancement of the focusing effect through the scattering medium and the resulting focusing performance of the present invention when the system is calibrated are shown in fig. 5. As shown in fig. 5 (a), this is a speckle formed by irradiating light emitted from the SLM without modulation (loading random phase) onto a scattering medium with a moderate scattering coefficient (such as a frosted card), and this speckle background is used as a control. As in fig. 5 (b), which is the focus obtained through the medium using the DOPC system without any calibration, the PBR is only 60. As shown in fig. 5 (c), after the primary pixel matching is completed, the focal point PBR formed by the DOPC through the focusing thereof is about 200. However, after the mechanical calibration of the six degrees of freedom SLM pose is completed, the focus PBR is lifted hundreds of times as much as about 6×10 as in fig. 5 (d) 4 . Through inspection, delta theta x And delta theta y The final precision of (2) is 0.0005 DEG, delta theta z The final precision of (a) is 0.02 DEG, the most significant of Deltax and DeltayThe final precision was 4 μm and the final precision of Δz was 50 μm. After compensation of the system wave aberration is completed using the zernike polynomials, the focus PBR is further raised to 1.1×10 as shown in fig. 5 (e) 5 Reaching 70% of the theoretical limit.
As in fig. 6 (a) for the speckle obtained by not loading the SLM with the modulating phase, fig. 6 (b) - (d) are the foci obtained inside the medium for iterations 1, 3, 5, respectively.
It is to be understood that the above examples of the present invention are provided by way of illustration only and not by way of limitation of the embodiments of the present invention. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. Any modification, equivalent replacement, improvement, etc. which come within the spirit and principles of the invention are desired to be protected by the following claims.

Claims (10)

1. The near infrared deep tissue focusing system based on rapid mechanical calibration is characterized by comprising a control device, a laser (1), a pose adjusting device (2), a first unpolarized beam splitting cube (31), a second unpolarized beam splitting cube (32), a third unpolarized beam splitting cube (33), a first image sensor (4) and a spatial light modulator (5), wherein the first image sensor (4) and the spatial light modulator (5) are respectively arranged at the symmetrical positions of the reflecting surfaces of the first unpolarized beam splitting cube (31), the second unpolarized beam splitting cube (32) is arranged between the first unpolarized beam splitting cube (31) and the spatial light modulator (5), the third unpolarized beam splitting cube (33) is arranged between the first unpolarized beam splitting cube (31) and the first image sensor (4), the laser (1) and the first unpolarized beam splitting cube (31), the second unpolarized beam splitting cube (32) and the third unpolarized beam splitting cube (33) are respectively arranged at the symmetrical positions of the reflecting surfaces of the first unpolarized beam splitting cube (31), the second unpolarized beam splitting cube (32) and the spatial light modulator (5), and the third unpolarized beam splitting cube (33) are respectively arranged between the first unpolarized beam splitting cube (31) and the first unpolarized beam splitting cube (4), and the position adjusting device (33) is arranged on the unpolarized beam splitting cube (9), and the position adjusting device is arranged on the unpolarized beam splitting cube (3) and the position adjusting device The pose adjusting device (2) and the first image sensor (4) are electrically connected;
The optical fiber reflection type light source device comprises a light source device, and is characterized by further comprising a pixel matching system (6), wherein the pixel matching system (6) comprises a pair of first lenses (61) and a pair of reflecting mirrors (91), each reflecting mirror (91) comprises a first reflecting mirror (62) and a second reflecting mirror (63), the first reflecting mirrors (62) and a first unpolarized beam splitting cube (31) are respectively positioned at two ends of an optical axis of the pair of lenses, and a reflecting surface of the second reflecting mirror (63) is aligned with one side of the second unpolarized beam splitting cube (32).
The optical path adjusting device is characterized by further comprising a focusing system (7) arranged between the first unpolarized beam splitting cube (31) and the optical path adjusting structure (9), wherein the focusing system (7) comprises a second lens (71), a medium fixing structure, a fourth unpolarized beam splitting cube (72) and a second image sensor (73) arranged between the first unpolarized beam splitting cube (31) and the optical path adjusting structure (9), the second lens (71), the medium fixing structure and the fourth unpolarized beam splitting cube (72) are sequentially arranged, the optical path adjusting structure (9) is positioned on the other side of the fourth unpolarized beam splitting cube (72) relative to the medium fixing structure, and the second image sensor (73) and the medium fixing structure are respectively positioned on the symmetrical positions of the reflecting surfaces of the fourth unpolarized beam splitting cube (72).
2. The near infrared deep tissue focusing system based on rapid mechanical calibration of claim 1, further comprising an ultrasound focusing system (8), the ultrasound focusing system (8) comprising an ultrasound transducer (81) and a light blocking structure (82), the ultrasound transducer (81) being disposed between the medium fixation structure and the fourth unpolarized beam splitting cube (72), the light blocking structure (82) being configured to allow or block light to pass between the fourth unpolarized beam splitting cube (72) and the light path adjustment structure (9).
3. The near infrared deep tissue focusing system based on rapid mechanical calibration of claim 2, wherein the ultrasonic focusing system (8) further comprises a transparent water tank (83), the fourth unpolarized beam splitting cubes (72) are all designed and arranged in the transparent water tank (83), the focal point of the ultrasonic transducer (81) is arranged in the transparent water tank (83), and a semi-transparent reflector (84) is arranged between the focal point of the ultrasonic transducer (81) and the fourth unpolarized beam splitting cubes (72).
4. The near infrared deep tissue focusing system based on rapid mechanical alignment of claim 1, wherein the optical path adjustment structure (9) comprises a mirror (91) that causes laser light emitted by the laser (1) to enter into the second unpolarized beam splitting cube (32), a half-wave plate (92) located on the laser light path, a first beam expanding structure (93) located between the half-wave plate (92) and the second unpolarized beam splitting cube (32);
The optical path adjusting structure (9) further comprises a fifth unpolarized beam splitting cube (94) for splitting laser emitted by the laser (1), an acousto-optic modulator (95) and a second beam expanding structure (96) which are sequentially arranged in the direction of reflected light of the fifth unpolarized beam splitting cube, and an acousto-optic modulator (95) arranged between the third unpolarized beam splitting cube (33) and the half-wave plate (92), wherein the half-wave plate (92) is arranged in the incident and reflecting directions of the fifth unpolarized beam splitting cube (94).
The optical path adjusting structure (9) further comprises a sixth unpolarized beam splitting cube (97) for splitting laser emitted by the laser (1), an acousto-optic modulator (95) arranged between the fourth unpolarized beam splitting cube (72) and the sixth unpolarized beam splitting cube (97), and an acousto-optic modulator (95) arranged between the sixth unpolarized beam splitting cube (97) and the half-wave plate (92), and half-wave plates (92) are arranged on the incidence and reflection directions of the sixth unpolarized beam splitting cube (97).
5. The near infrared deep tissue focusing method based on the rapid mechanical calibration is characterized by comprising the following steps of:
s1: the reference light formed by the light emitted by the laser (1) after passing through the light path adjusting structure (9) causes the reference light to interfere with the reflected light of the spatial light modulator (5), so that the image generated by the spatial light modulator (5) has a specific interference pattern;
S2: adjusting the pose adjustment device (2) such that Δx, Δy, Δz and Δθ of the spatial light modulator (5) are adjusted z Coarse adjustment is performed in four degrees of freedom, so that the first image sensor (4) senses an image generated by the spatial light modulator (5) and the image generated by the spatial light modulator (5) corresponds to each pixel of the first image sensor (4);
s3: placing a scattering medium in the medium fixing structure so that the reference light and the sample light passing through the scattering medium form heterodyne interference, continuously recording a plurality of frames of interference patterns recognized by the first image sensor (4) by the control device, calculating a phase diagram, loading the calculated phase diagram on the spatial light modulator (5) to enable light beams to reversely penetrate the scattering medium, reforming parallel light beams entering the sample, and focusing on the second image sensor (73);
s4: the control device controls the pose adjustment device (2) to control the delta x, delta y, delta z and delta theta of the spatial light modulator (5) x 、Δθ y 、Δθ z The six degrees of freedom are regulated one by one, and the control device records the peak intensity of the focus in the image identified by the second image sensor (73) and the coordinate position and angle of the corresponding spatial light modulator (5) to obtain the optimal pose of the spatial light modulator (5).
6. The near infrared deep tissue focusing method based on rapid mechanical calibration of claim 5, further comprising the steps of:
Adjusting the frequency of the acousto-optic modulator (95) to f US And the beat frequency f of the two M At 10Hz, heterodyne interference is formed between the sample light and the reference light generated by the acousto-optic modulator, the first image sensor (4) is a scientific CMOS camera, the second image sensor (73) is an industrial CMOS camera, and the frame rate of the scientific CMOS camera is set to be 4f M After continuously recording 4 frames of interference patterns, the conjugate of the calculated phase diagram is loaded on a spatial light modulator (5) to enable the light beam to reversely penetrate through a scattering medium, and a parallel light beam which is injected into a sample is reformed and focused on an industrial gradeOn a CMOS camera.
7. The near infrared deep tissue focusing method based on rapid mechanical calibration of claim 5, further comprising the steps of:
s5: and (3) taking a multi-order Zernike polynomial, scanning each order coefficient in the order from low order to high order, feeding back the focus peak intensity of the second image sensor (73) to obtain each order optimal coefficient, and superposing a final Zernike compensation phase diagram on the conjugate phase diagram in the step S3.
8. The near infrared deep tissue focusing method based on rapid mechanical calibration of claim 7, wherein the step S5 further comprises the steps of:
In the step S5, 8-order Zernike polynomials are taken; the scanning range of each order coefficient is [ -2,2], and the stepping precision is 0.01.
9. The near infrared deep tissue focusing method based on rapid mechanical calibration of any one of claims 6 to 8, further comprising the steps of:
s6: the ultrasonic transducer (81) emits ultrasonic beams into the scattering medium, the incident light of the scattering medium passes through an ultrasonic intersection point to enable partial reflected light to shift in frequency, then heterodyne interference is carried out on the reference light generated by the laser (1) and the partial reflected light to detect the partial reflected light, and finally the control device inverts the reflected light passing through an ultrasonic focus to focus in the scattering medium.
10. The near infrared deep tissue focusing method based on rapid mechanical calibration of claim 1, further comprising the steps of:
s7: and performing multiple iterations on the inverted light as incident light of the scattering medium.
CN202310608816.1A 2023-04-24 2023-05-26 Near infrared deep tissue focusing system and method based on rapid mechanical calibration Pending CN116793988A (en)

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