CN115553723A - Correlated imaging method based on high-speed modulation random medium doped optical fiber for abnormal cell screening in blood - Google Patents
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Abstract
The invention discloses a high-speed modulation random medium doped optical fiber-based correlation imaging method for screening abnormal cells in blood. The method can realize the modulation of the hundred megahertz rate of an incident light field by modulating the random medium in the random medium doped optical fiber. The method mainly comprises the following steps: modulating random media at low speed, and prefabricating reference light; modulating random medium at high speed, and recording object optical signal; and performing correlation calculation to obtain an imaging result. The invention solves the problem that the abnormal cells in blood need to be screened at extremely high modulation frequency based on the correlation imaging.
Description
Technical Field
The invention relates to the field of microscopic correlation imaging, in particular to a correlation imaging method based on a high-speed modulation random medium doped optical fiber for screening abnormal cells in blood.
Background
Correlated imaging, also known as ghost imaging, is a rapid method of computational imaging that has developed in recent years. For correlated imaging with classical light sources, the basic principle is: the laser source is modulated by a modulation device into a pseudo-thermal optical field (also called speckle field) with space-time fluctuation distribution, and then is divided into two same beams of light by a beam splitting device, wherein one beam of light is called object light, and the total light intensity of the beam of light is received by a photoelectric detector without space resolution capability after the beam of light interacts with an object; the other beam of light is called reference light, and the light intensity distribution of the other beam of light is recorded by an area array detector with spatial resolution; and finally, performing correlation calculation on the two detected signals after multiple sampling to obtain an image of the object. The mode that the two paths of light are subjected to correlation calculation and then imaged enables correlation imaging to exert unique advantages in the field of microscopic imaging. Reference 1: wu Ziwen, qiu Xiaodong, chen Lixiang. State of the art in relation to imaging and vision [ J ] laser and optoelectronics development, 2020,57 (06): 9-25.
There are now methods for microscopic imaging using correlated imaging, particularly methods for screening for abnormal cells in blood in conjunction with optical fibers. However, the arterial flow velocity of human blood is about 40cm/s, the venous flow velocity is about 15cm/s, and even if venous blood is taken as an object of associated imaging, the modulation frequency required for modulating the light source is in the order of hundreds of MHz. The traditional modulation devices such as ground glass, a liquid crystal spatial light modulator and a Digital Micromirror Device (DMD) rotating at high speed have modulation frequencies of hundreds of Hz, kHz and tens of kHz respectively, and all three modulation frequencies can not reach the modulation frequency required by blood cell imaging screening. Therefore, a novel, high-speed and stable light source modulation method is provided, which is necessary for abnormal cell screening in blood based on correlated imaging. Reference 2: zhu Xiaohui, fu Xiquan, bai Yanfeng a screening system for non-stop flow imaging of abnormal cells in blood vessels based on correlated imaging [ P ]. Hunan province: CN114376528A, 2022-04-22; reference 3: liu C, liu J, chen J. High frame-rate computing system using an optical fiber array and a low-pixel APD array [ J ]. Optics Express,2018,26 (8): 10048.
Random media are random solid particles capable of producing electro-optic, acousto-optic or magneto-optic effects. The random medium is relatively independent and can be modulated by external control, and the electro-optic, acousto-optic or magneto-optic modulation frequency can reach hundreds of MHZ and even GHz, so that the high-speed modulation of an optical field is facilitated. Optical fibers are widely used as an excellent optical transmission medium in the fields of optical communication, biomedical imaging and the like. Therefore, the random medium is doped at the emergent end of the optical fiber, and the random medium is modulated at high speed through external control, so that the requirement of high modulation frequency for screening abnormal cells in actual flowing blood through correlated imaging can be met.
Disclosure of Invention
The invention aims to solve the problem that the abnormal cells in blood need to be screened at a very high modulation rate without stopping flow imaging based on correlated imaging.
In order to achieve the purpose, the invention provides the following technical scheme:
an associated imaging method based on high-speed modulation random medium doped optical fiber for abnormal cell screening in blood is characterized in that the method uses a device comprising: the device comprises a laser source (1), an optical fiber coupling system (2), a random medium doped optical fiber (3), a high-speed modulation random medium control system (4), an optical fiber beam splitting system (5), a multimode optical fiber (6-1), a multimode optical fiber (6-2), a reference light collecting system (7) and an object light collecting system (8). The high-speed modulation random medium control system (4) can realize low-speed and high-speed modulation of the random medium doped optical fiber (3), and meets the requirement of abnormal cell screening in blood based on associated imaging.
The laser source (1) is used for generating laser with good space-time coherence.
The optical fiber coupling system (2) is arranged behind the laser source (1) and used for coupling laser into the random medium doped optical fiber (3).
The random medium doped optical fiber (3) is arranged behind the optical fiber coupling system (2) and consists of a random medium (3-1) and a multimode optical fiber (3-2), and the modulation of an incident optical field is realized by modulating the random medium (3-1).
And the high-speed modulation random medium control system (4) is connected with the random medium (3-1) and is used for controlling the modulation of the random medium (3-1).
The optical fiber beam splitting system (5) is arranged at the emergent end of the random medium doped optical fiber (3) and is used for splitting the light field modulated by the random medium doped optical fiber (3) into two beams of light with the same light intensity distribution and respectively transmitting the two beams of light to the multimode optical fiber (6-1) and the multimode optical fiber (6-2).
The multimode optical fiber (6-1) is connected with one emergent end of the optical fiber beam splitting system (5), and the light field pattern of the emergent end is collected by the reference light collecting system (7).
The multimode optical fiber (6-2) is connected with the other emergent end of the optical fiber beam splitting system (5), and the emergent end of the multimode optical fiber is inserted into a blood vessel.
The reference light collection system (7) is used for collecting the light intensity distribution of the emergent end of the multimode optical fiber (6-1) and using the light intensity distribution as a reference light signal in the associated imaging.
The object light acquisition system (8) is used for acquiring optical signals scattered after the light field emitted by the multimode optical fiber (6-2) irradiates cells in the blood vessel, and the optical signals are used as object light signals in the correlated imaging.
And the correlation calculation module (9) is used for performing correlation calculation on the acquired signals.
The modulation of the random medium (3-1) is controllable and repeatable, i.e. the same random modulation can be performed multiple times; therefore, the random medium (3-1) cannot be doped too much, and is preferably doped in a small range of the incident end of the multimode fiber (3-2). The multimode optical fiber (3-2) in the random medium doped optical fiber (3) has an optical waveguide function, so that the length thereof is not particularly limited. But the material, core and cladding diameters and lengths of the multimode fibers (6-1) and (6-2) are all the same to ensure that the speckle pattern collected by the reference light collection system (7) is the same as that incident on the blood. In order to minimize the different losses caused by the multimode fibers (6-1) and (6-2) in transmission, the lengths of the two multimode fibers should be as short as possible, about 1-10cm.
Suppose that N data records are required for each correlation imaging, i.e., N reference light and object light signals are required to produce one single correlation imaging result. We can repeat this process M times, i.e. imaging the flowing blood cells M times during one blood circulation. And (5) screening the cells with abnormal characteristics by analyzing the imaging results of M times.
Generally, the frame rate of a detector with spatial resolution in the reference light collection system (7) is very low, and the light field under high-speed modulation cannot be recorded, but a detector without spatial resolution in the object light collection system (8) can record signals under high-speed modulation. Therefore, it is necessary to perform the reference optical signal at a low speed and then perform the object optical signal acquisition at a high speed. The imaging process can be divided into four steps.
Step 1, a high-speed modulation random medium control system (4) performs low-speed modulation on a random medium (3-1), simultaneously a reference light collection system records the light field of the emergent end of the multimode optical fiber (6-1) after each modulation, and records signals N x M times, wherein the meanings of N and M are as described above. This stage is performed once by acquiring the reference light signal in advance. If the random medium doped fiber (3) is disturbed by the outside to change the initial state, the process is repeated.
And 2, the high-speed modulation random medium control system (4) performs high-speed modulation on the random medium (3-2), the modulation mode is completely the same as that at the low speed, but the speed is increased, and the modulated light field is inserted into a blood vessel after passing through the multimode optical fiber (6-2) and then irradiates on blood cells to be imaged. Meanwhile, the object light collecting system collects scattered light scattered by blood cells, blood vessels and surrounding tissues. Similarly, the object light collection system also records N × M signals. One imaging may be performed each time a signal is acquired N times. The phase is a real-time signal light acquisition imaging phase and should be entered after the prefabrication phase is completed.
And 3, for single-time correlated imaging, adopting a public correlated imaging formula, wherein the second-order fluctuation correlated imaging formula is as follows:
in the formula, G (x, y) is a single correlation imaging result, and x and y are two-dimensional image coordinates; n is the collection frequency; i is i (x,y)、B i Respectively an ith reference light signal and an object light signal in the N signals imaged at this time;<I>and<B>the average values of the N reference light signals and the object light signals of the imaging are respectively.
And 4, repeating the step 3M times to obtain M associated imaging results.
Compared with the prior art, the invention has the following technical effects: the invention provides a high-speed modulation random medium doped optical fiber-based correlation imaging method for screening abnormal cells in blood. Thereby meeting the requirement of rapidly screening all the cancerated cells in the blood circulation of the human body in real time without stopping the flow. The invention solves the problem that the abnormal cells in blood need to be screened based on the correlation imaging, and the system modulation frequency can reach at least hundred MHz.
Drawings
Fig. 1 is a schematic diagram of a high-speed modulation random medium doped optical fiber-based correlation imaging method for abnormal cell screening in blood provided in an embodiment of the present invention.
1. A laser source; 2. a fiber optic coupling system; 3. 3-1 parts of random medium doped optical fiber, 3-2 parts of random medium and multimode optical fiber; 4. a high-speed modulated random media control system; 5. an optical fiber beam splitting system; 6-1, multimode optical fiber, 6-2 and multimode optical fiber; 7. the device comprises a reference light acquisition system, 7-1, an imaging lens, 7-2 and an area array CCD detector; 8. an object light collection system 8-1, a collection lens 8-2 and a photomultiplier; 9. and a correlation calculation module.
Detailed Description
Fig. 1 is a schematic diagram of a high-speed modulation random medium doped optical fiber-based correlation imaging method for abnormal cell screening in blood provided in an embodiment of the present invention. The laser source 1 generates laser which is coupled into the random medium doped fiber 3 after passing through the fiber coupling system 2. The high-speed modulation random medium control system 4 controls the modulation of the random medium 3-1, and the modulated light field is transmitted by the multimode optical fiber 3-2 and then is divided into two beams of light with the same light intensity distribution by the optical fiber beam splitting system 5. One beam of light is collected by the reference light collection system 7 after passing through the multimode optical fiber 6-1, the other beam of light is irradiated on blood cells to be imaged after passing through the multimode optical fiber 6-2, and the object light collection system 8 collects light scattered by the blood cells, blood vessels and surrounding tissues. Finally, imaging is carried out through the correlation calculation module 9.
The laser 1 is a solid laser with the wavelength of 532 nm. The random medium doped fiber 3 is a multimode fiber 3-2 with an incident end doped with a random medium 3-1. The random medium 3-1 is a random solid particle capable of producing electro-optic, acousto-optic or magneto-optic effects. The high-speed modulation random medium control system 4 is an electronic circuit control system necessary for high-speed modulation of the random medium 3-1. The optical fiber beam splitting system 5 is an optical fiber beam splitter. The multimode optical fiber 6-1 and the multimode optical fiber 6-2 are two common step-index multimode optical fibers with the same length of 2 cm. The reference light collection system 7 is composed of an imaging lens 7-1 and an area array CCD detector 7-2. The imaging lens 7-1 images the light field at the emergent end of the multimode optical fiber 6-1 onto the area array CCD detector 7-2. The object light collection system 8 is composed of a collection lens 8-1 and a photomultiplier tube 8-2. The collecting lens 8-1 collects the light scattered by the menstrual blood cells, blood vessels and surrounding tissues to the photomultiplier tube 8-2.
The specific flow of the correlated imaging method based on the high-speed modulation random medium doped optical fiber for screening abnormal cells in blood is as follows:
step 1: laser emitted by a laser source 1 is coupled to a random medium doped fiber 3 through a fiber coupling system 2, and a high-speed modulation random medium control system 4 firstly performs low-speed modulation on a random medium 3-1. The modulated light field is transmitted by multimode optical fiber 3-2 and then divided into two beams of light with the same light intensity distribution by optical fiber beam splitting system 5, and only multimode optical fiber 6-1 connected with reference light collection system 7 is considered. The reference light collection system 7 collects the light field of the emergent end of the multimode optical fiber 6-1. Assuming that N =10000 data are needed for each single correlated imaging, M correlated imaging is needed for imaging screening of most blood cells in blood vessels, the selection of M is related to the screening precision, and the larger M, the more sufficient the blood cells are sampled, and the higher the screening precision. The reference light collection system 7 therefore needs to collect N x M modulated light field patterns.
Step 2: laser emitted by the laser source 1 is coupled to the random medium doped fiber 3 after passing through the fiber coupling system 2, and the high-speed modulation random medium control system 4 performs high-speed modulation on the random medium 3-1 to ensure that blood cells can be approximately regarded as static during single correlated imaging. The modulated light field is transmitted through multimode optical fiber 3-2 and then is split into two beams of light with the same light intensity distribution by optical fiber beam splitting system 5, now only multimode optical fiber 6-2 inserted into the blood vessel is considered. Then, the scattered light from the blood cells and blood vessels and their surroundings is collected by the collecting lens 8-1 in the object light collecting system 8, and then the intensity of the collected scattered light is recorded by the photomultiplier tube 8-2. N x M object light data were also collected.
And step 3: and calculating every N acquired reference light and object light data by using the second-order fluctuation correlation imaging formula to obtain an image about the intravascular blood cells.
And 4, step 4: repeating step 3M times to obtain M images of blood cells at different positions in the blood vessel. The abnormal cells in the blood are screened by detecting the cells with abnormal characteristics in the image.
The above-mentioned embodiments are merely practical examples of the present invention, and do not limit the present invention in any way. Any person skilled in the art can make several variations and modifications according to the core idea of the present invention, and all such variations and modifications fall within the scope of protection of the present application.
Claims (9)
1. An associated imaging method based on high-speed modulation random medium doped optical fiber for abnormal cell screening in blood is characterized in that the method uses a device comprising: the device comprises a laser source (1), an optical fiber coupling system (2), a random medium doped optical fiber (3), a high-speed modulation random medium control system (4), an optical fiber beam splitting system (5), a multimode optical fiber (6-1), a multimode optical fiber (6-2), a reference light acquisition system (7), an object light acquisition system (8) and a correlation calculation module (9); the high-speed modulation random medium control system (4) can realize low-speed and high-speed modulation on the random medium doped optical fiber (3), and meets the requirement of abnormal cell screening in blood based on associated imaging;
the laser source (1) is used for generating laser with good space-time coherence;
the optical fiber coupling system (2) is arranged behind the laser source (1) and is used for coupling laser into the random medium doped optical fiber (3);
the random medium doped optical fiber (3) is arranged behind the optical fiber coupling system (2) and consists of a random medium (3-1) and a multimode optical fiber (3-2), and the modulation of an incident light field is realized by modulating the random medium (3-1);
the high-speed modulation random medium control system (4) is connected with the random medium (3-1) and is used for controlling the modulation of the random medium (3-1);
the optical fiber beam splitting system (5) is arranged at the emergent end of the random medium doped optical fiber (3) and is used for splitting the light field modulated by the random medium doped optical fiber (3) into two beams of light with the same light intensity distribution and respectively transmitting the two beams of light to the multimode optical fiber (6-1) and the multimode optical fiber (6-2);
the multimode optical fiber (6-1) is connected with one emergent end of the optical fiber beam splitting system (5), and the light field pattern of the emergent end is collected by a reference light collecting system (7);
the multimode optical fiber (6-2) is connected with the other emergent end of the optical fiber beam splitting system (5), and the emergent end of the multimode optical fiber is inserted into a blood vessel;
the reference light acquisition system (7) is used for acquiring the light intensity distribution of the emergent end of the multimode optical fiber (6-1) and taking the light intensity distribution as a reference light signal in the associated imaging;
the object light acquisition system (8) is used for acquiring optical signals scattered after an emergent light field of the multimode optical fiber (6-2) irradiates cells in a blood vessel, and the optical signals are used as object light signals in associated imaging;
the correlation calculation module (9) is used for performing correlation calculation on the acquired signals;
the specific flow of the correlated imaging method based on the high-speed modulation random medium doped optical fiber for screening abnormal cells in blood is as follows:
step 1, a high-speed modulation random medium control system (4) modulates a random medium (3-1) at a low speed to realize low-speed modulation of an incident light field, and simultaneously, a reference light collection system records an emergent light field after each modulation and records N × M signals; n is the number of measurement times required by single correlated imaging, and M is the total correlated imaging number of the system;
step 2, stopping modulating the random medium (3-1), and after the random medium (3-1) is recovered to the initial state, modulating the random medium (3-1) at a high speed by a high-speed modulation random medium control system (4) to realize high-speed modulation of an incident light field; meanwhile, an object light collecting system (8) collects scattered light scattered by blood cells, blood vessels and surrounding tissues and records N x M signals; every time N times of signals are acquired, imaging can be carried out through the correlation calculation module (9);
step 3, for single correlated imaging, a public correlated imaging formula can be adopted, for example, the second-order fluctuation correlated imaging formula is:
in the formula, G (x, y) is a single correlation imaging result, and x and y are two-dimensional image coordinates; n is the collection times; i is i (x,y)、B i Respectively an ith reference light signal and an object light signal in the N signals imaged at this time;<I>and<B>respectively mean values of the N reference light signals and the object light signals of the imaging;
and 4, repeating the step 3 for M times to obtain M associated imaging results.
2. The correlated imaging method based on high speed modulation random medium doped fiber for abnormal cells screening in blood according to claim 1, wherein the wavelength of the laser source (1) is in the visible or infrared band.
3. The high-speed modulation random medium doped fiber-based correlated imaging method for abnormal cell screening in blood as claimed in claim 1, wherein said fiber coupling system (2) is a single lens or other device capable of coupling a laser source into an optical fiber.
4. The correlated imaging method based on high speed modulation random medium doped fiber for abnormal cell screening in blood according to claim 1, wherein the random medium (3-1) in the random medium doped fiber (3) is in the light incident end of the multimode fiber (3-2); random media are random solid particles capable of producing electro-optic, acousto-optic or magneto-optic effects.
5. The correlated imaging method based on high speed modulation random media doped fiber for abnormal cells screening in blood of claim 1, wherein the high speed modulation random media control system (4) is the necessary electronic circuit control system for high speed modulation of random media (3-1).
6. The correlated imaging method based on high-speed modulation random medium doped optical fiber for abnormal cell screening in blood as claimed in claim 1, wherein said optical fiber beam splitting system (5) is an optical device capable of splitting the incident light into two beams with the same optical field distribution.
7. The correlated imaging method based on high-speed modulation random medium doped fiber for abnormal cell screening in blood as claimed in claim 1, wherein said multimode fiber (6-1) and multimode fiber (6-2) are two same multimode fibers, which can be step index fiber, gradient index fiber or special fiber.
8. The correlated imaging method based on high-speed modulation random medium doped fiber for abnormal cell screening in blood as claimed in claim 1, wherein said reference light collection system (7) comprises an imaging lens (7-1) and a CCD or CMOS device (7-2) with spatial resolution capability.
9. A high speed modulation random medium doped fiber based correlated imaging method for abnormal cell screening in blood as claimed in claim 1 wherein said object light collection system (8) comprises a collection lens (8-1) and a photodiode or photomultiplier tube (8-2) without spatial resolution capability.
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