CN115553723B - High-speed modulation random medium doped optical fiber-based associated imaging method for screening abnormal cells in blood - Google Patents
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- 239000013307 optical fiber Substances 0.000 title claims abstract description 106
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- 210000004027 cell Anatomy 0.000 claims description 31
- 239000000835 fiber Substances 0.000 claims description 17
- 210000000601 blood cell Anatomy 0.000 claims description 14
- 210000004204 blood vessel Anatomy 0.000 claims description 14
- 230000008878 coupling Effects 0.000 claims description 14
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- 238000005859 coupling reaction Methods 0.000 claims description 14
- 230000000694 effects Effects 0.000 claims description 5
- 239000002245 particle Substances 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- 230000002175 menstrual effect Effects 0.000 claims description 3
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- A—HUMAN NECESSITIES
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Abstract
The invention discloses a correlation imaging method based on high-speed modulation random medium doped optical fiber for screening abnormal cells in blood. According to the method, the modulation of the hundred megahertz rate of an incident light field can be realized by modulating the random medium in the random medium doped optical fiber. The main flow of the method comprises the following steps: low-speed modulating random medium, prefabricating reference light; high-speed modulating random medium, recording object optical signal; and obtaining an imaging result through association calculation. The invention solves the problem that extremely high modulation frequency is required when abnormal cells in blood are screened based on correlated imaging.
Description
Technical Field
The invention relates to the field of microscopic association imaging, in particular to an association imaging method based on high-speed modulation random medium doped optical fibers for screening abnormal cells in blood.
Background
Correlated imaging, also known as ghost imaging, has evolved in recent years to provide a computational imaging method. For the correlated imaging with classical light sources, the basic principle is: the laser source is modulated into a pseudo thermal light field (also called a speckle field) with space-time fluctuation distribution by a modulating device, and then the pseudo thermal light field is divided into two identical beams of light by a beam splitting device, wherein one beam of light is called object light, and the object light interacts with an object and then is received by a photoelectric detector without space resolution capability; 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 capability; and finally, carrying out correlation calculation on the two paths of detected signals after multiple sampling to obtain an image of the object. The two paths of light can bring unique advantages into play in the microscopic imaging field through the mode of correlation calculation and then imaging. Reference 1: wu Ziwen, xiaodong, chen Lixiang. Related imaging state of the art and hope [ J ]. Laser and optoelectronics progress 2020,57 (06): 9-25.
Methods for microscopic imaging using correlated imaging, particularly methods for screening for abnormal cells in blood in combination with optical fibers, are now available. But the arterial flow rate of human blood is about 40cm/s and the venous flow rate is about 15cm/s, even though venous blood is the subject of the associated imaging, the modulation frequency required for modulating the light source is in the order of hundred MHz. Traditional modulation devices such as frosted glass, liquid crystal spatial light modulator and Digital Micromirror Device (DMD) rotating at high speed have modulation frequencies of hundred Hz, kHz and tens of kHz respectively, and all three cannot reach the modulation frequency required for imaging and screening blood cells. Therefore, a brand new high-speed stable light source modulation method is provided, which is necessary for screening abnormal cells in blood based on correlated imaging. Reference 2: zhu Xiaohui, fu Xiquan, bai Yanfeng. An imaging screening system based on correlated imaging of abnormal cells in vessels [ P ]. Hunan province: CN114376528a, 2022-04-22; reference to the literature 3：Liu C,Liu J,Chen J.High frame-rate computational ghost imaging system using an optical fiber phased 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 independent and can be modulated by external control, and the frequency of electro-optic, acousto-optic or magneto-optic modulation can reach hundred MHz and even GHz, which is very beneficial to high-speed modulation of the optical field. The optical fiber is used as an excellent optical transmission medium and is widely applied to 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 a high speed by external control, so that the requirement of extremely high modulation frequency required by the screening of abnormal cells in the actual flowing blood by correlated imaging can be met.
Disclosure of Invention
The invention aims to solve the problem that an extremely high modulation rate is required when abnormal cells in blood are subjected to continuous flow imaging screening based on correlated imaging.
In order to achieve the above purpose, the present invention provides the following technical solutions:
A high-speed modulated random medium doped fiber-based associated imaging method for screening abnormal cells in blood, the method 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 meet the requirements of abnormal cell screening in blood based on correlation 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 a random solid particle capable of generating electro-optic, acousto-optic or magneto-optic effect, is arranged in the optical fiber coupling system (2) and consists of a random medium (3-1) and a multimode optical fiber (3-2), and modulates an incident light field by modulating the random medium (3-1); the random medium (3-1) in the random medium doped optical fiber (3) is arranged in the light incident end of the multimode optical fiber (3-2).
The high-speed modulation random medium control system (4) is an electronic circuit control system which is necessary for carrying out high-speed modulation on the random medium (3-1), is connected with the random medium (3-1) and is used for controlling the modulation on 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 optical field modulated by the random medium doped optical fiber (3) into two beams of light with the same light intensity distribution and transmitting the two beams of light to the multimode optical fiber (6-1) and the multimode optical fiber (6-2) respectively.
The multimode optical fiber (6-1) is connected with an 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 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 correlated imaging.
The object light collection system (8) is used for collecting light signals scattered by cells in the blood vessel after the emergent light field of the multimode optical fiber (6-2) irradiates the cells, and taking the light signals as object light signals in the associated imaging.
The correlation calculation module (9) is used for performing correlation calculation on the acquired signals.
The modulation of the random medium (3-1) has controllability and repeatability, namely the same random modulation can be carried out for a plurality of times; the random medium (3-1) is therefore not too doped, preferably within a small range of the entrance end of the multimode optical fiber (3-2). The multimode optical fiber (3-2) of the random medium doped optical fiber (3) has an optical waveguide function, so its length is not particularly limited. However, the material, core and cladding diameters and lengths of the multimode fibers (6-1) and (6-2) should be 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 optical fiber (6-1) and the multimode optical fiber (6-2) during transmission, the lengths of the two multimode optical fibers should be as short as possible, about 1-10cm.
It is assumed that N data needs to be recorded for each correlated imaging, i.e. N reference light and object light signals are required to produce a single correlated imaging result. We can repeat this process M times, i.e. imaging the flowing blood cells M times during one blood circulation. Cells with abnormal characteristics were screened by analyzing the M imaging results.
Generally, the frame rate of a detector with spatial resolution in the reference light collection system (7) is very low, and a 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, the reference optical signal needs to be prefabricated at a low speed, and then the object optical signal needs to be collected at a high speed. The imaging process can be divided into four steps.
Step 1, a high-speed modulation random medium control system (4) carries out low-speed modulation on the random medium (3-1), and meanwhile, a reference light acquisition system records the light field at the emergent end of the multimode optical fiber (6-1) after each modulation, and N is recorded for M times, wherein the meanings of N and M are as described above. This stage is to collect the reference light signal in advance, only once. If the random medium doped fiber (3) is subject to external disturbance to change its initial state, this stage is re-performed.
And 2, a high-speed modulation random medium control system (4) carries out high-speed modulation on the random medium (3-2), the modulation mode is completely the same as that of low-speed modulation, the speed is only increased, and at the moment, the modulated light field is inserted into a blood vessel after passing through a multimode optical fiber (6-2) and then irradiated onto blood cells to be imaged. At the same time, the object light collecting system collects scattered light after scattering of menstrual blood cells and blood vessels and surrounding tissues. Likewise, the object light collection system also records N x M signals. Imaging may be performed once every N times a signal is acquired. The stage is a real-time signal light acquisition imaging stage, and the stage is needed to be entered after the prefabrication stage is completed.
Step 3, for single correlated imaging, a disclosed correlated imaging formula is adopted, and a second-order fluctuation correlated imaging formula is as follows:
Wherein G (x, y) is a single correlation imaging result, and x, y are two-dimensional image coordinates; n is the collection times; i i(x,y)、Bi is the ith reference light and object light signal in the N signals imaged at this time respectively; < I > and < B > are the average of the N reference light and object light signals of the current imaging, respectively.
And 4, repeating the step 3 for M times to obtain M associated imaging results.
Compared with the prior art, the invention has the following technical effects: the invention provides a correlation imaging method based on a high-speed modulation random medium doped optical fiber for screening abnormal cells in blood, which is used for modulating an incident light field by carrying out low-speed and high-speed modulation on the random medium in the random medium doped optical fiber, wherein the high-speed modulation frequency is at least hundred MHz, and the optical fiber is used as a medium for light transmission in the system and forms a laser speckle pattern for illuminating the blood. Thereby meeting the requirement of continuously flowing and rapidly screening all cancerous cells in the blood circulation of the human body in real time. The invention solves the problem that extremely high modulation frequency is needed when abnormal cells in blood are screened based on correlated imaging, and the modulation frequency of the system can reach at least hundred MHz.
Drawings
FIG. 1 is a schematic illustration of a high-speed random medium doped fiber based correlated imaging method for abnormal cell screening in blood provided in an embodiment of the present invention.
1. A laser source; 2. an optical fiber coupling system; 3. 3-1 of random medium doped optical fiber, 3-2 of random medium and multimode optical fiber; 4. a high-speed modulation random medium control system; 5. an optical fiber beam splitting system; 6-1, multimode optical fiber, 6-2, multimode optical fiber; 7. the system comprises a reference light acquisition system, 7-1, an imaging lens, 7-2 and an area array CCD detector; 8. the object light collecting system comprises 8-1 parts of collecting lenses, 8-2 parts of photomultiplier tubes; 9. and an association calculation module.
Detailed Description
Fig. 1 is a schematic diagram of a related imaging method based on a high-speed modulated random medium doped fiber for abnormal cell screening in blood according to an embodiment of the present invention. The laser source 1 generates laser light which is coupled into the random medium doped optical fiber 3 after passing through the optical 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 split into two beams of light with identical light intensity distribution by the optical fiber beam splitting system 5. One beam of light is collected by a reference light collecting system 7 after passing through a multimode optical fiber 6-1, the other beam of light irradiates blood cells to be imaged after passing through a multimode optical fiber 6-2, and a thing light collecting system 8 collects light scattered by blood cells, blood vessels and surrounding tissues. Finally, imaging is performed by the association calculation module 9.
The laser 1 is a solid-state laser with a wavelength of 532 nm. The random medium doped optical fiber 3 is a multimode optical fiber 3-2 doped with a random medium 3-1 in the incident end. The random medium 3-1 is a random solid particle capable of producing an electro-optic, acousto-optic or magneto-optic effect. 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 fibers 6-1 and 6-2 are two common step-index multimode optical fibers with the same length of 2 cm. The reference light acquisition 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 exit 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 and blood vessels and surrounding tissues onto the photomultiplier tube 8-2.
The specific flow of the high-speed modulation random medium doped optical fiber-based associated imaging method for screening abnormal cells in blood is as follows:
Step 1: the laser emitted by the laser source 1 is coupled to the random medium doped optical fiber 3 through the optical fiber coupling system 2, and the high-speed random medium control system 4 firstly carries out low-speed modulation on the random medium 3-1. The modulated light field is transmitted by the multimode optical fiber 3-2 and then is divided into two beams of light with identical light intensity distribution by the optical fiber beam splitting system 5, and only the multimode optical fiber 6-1 connected with the reference light acquisition system 7 is considered. The reference light acquisition system 7 acquires the light field at the exit end of the multimode optical fiber 6-1. Assuming that n=10000 data are required for each single correlated imaging, M correlated imaging is required for imaging a large portion of blood cells in a blood vessel, where M is selected in relation to the screening accuracy, and the larger M is, the more sufficient the blood cells are sampled, and the higher the screening accuracy is. The reference light acquisition system 7 is therefore required to acquire n×m modulated light field patterns.
Step 2: the laser emitted by the laser source 1 is coupled to the random medium doped optical fiber 3 after passing through the optical fiber coupling system 2, and the random medium 3-1 is modulated at a high speed by the high-speed modulation random medium control system 4 so as to ensure that blood cells can be approximately regarded as static in single correlated imaging. The modulated light field is transmitted through the multimode optical fiber 3-2 and then split into two beams of light with identical light intensity distribution by the optical fiber splitting system 5, and only the multimode optical fiber 6-2 inserted into the blood vessel is considered. The scattered light from blood cells and blood vessels and their surroundings is then collected by a collection lens 8-1 in the object light collection system 8, and the intensity of the collected scattered light is recorded by a photomultiplier tube 8-2. N x M object light data were also collected.
Step 3: and calculating the acquired reference light data and object light data by using the second-order fluctuation correlation imaging formula to obtain an image about blood cells in the blood vessel.
Step 4: and (3) repeating the step (3) for M times to obtain images of blood cells at different positions in M blood vessels. The screening of abnormal cells in blood is achieved by detecting cells with abnormal characteristics in the image.
The above-described embodiments are merely practical examples of the present application and do not limit the present application in any way. Any person skilled in the art, based on the core idea of the application, shall make several variations and modifications that fall within the protection scope of the application.
Claims (7)
1. A high-speed modulated random medium doped fiber-based associated imaging method for screening abnormal cells in blood, the method comprising: the device comprises a laser source (1), an optical fiber coupling system (2), a random medium doping 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 an associated calculation module (9); 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 meet the requirements of abnormal cell screening in blood based on correlation 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 a random solid particle capable of generating electro-optic, acousto-optic or magneto-optic effect, is arranged in the optical fiber coupling system (2) and consists of a random medium (3-1) and a multimode optical fiber (3-2), and modulates an incident light field by modulating the random medium (3-1); the random medium (3-1) in the random medium doped optical fiber (3) is arranged in the light incidence end of the multimode optical fiber (3-2);
The high-speed modulation random medium control system (4) is an electronic circuit control system which is necessary for carrying out high-speed modulation on the random medium (3-1), is connected with the random medium (3-1) and is used for controlling the modulation on 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 dividing the optical field modulated by the random medium doped optical fiber (3) into two beams of light with the same light intensity distribution and transmitting the two beams of light to the multimode optical fiber (6-1) and the multimode optical fiber (6-2) respectively;
The multimode optical fiber (6-1) is connected with an 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 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 light signals scattered by cells in a blood vessel after the emergent light field of the multimode optical fiber (6-2) irradiates the cells, and taking the light signals as object light signals in the associated imaging;
The association calculation module (9) is used for carrying out association calculation on the acquired signals;
The specific flow of the high-speed modulation random medium doped optical fiber-based associated imaging method 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 acquisition system records an emergent light field after each modulation, and records N times of signals altogether; n is the number of measurement times required by single associated imaging, M is the total associated imaging times of the system;
Step 2, stopping modulating the random medium (3-1), and after the random medium (3-1) is restored to an initial state, modulating the random medium (3-1) at a high speed by a high-speed modulation random medium control system (4) so as to realize high-speed modulation of an incident light field; meanwhile, an object light collecting system (8) collects scattered light scattered by menstrual blood cells, blood vessels and surrounding tissues thereof, and records N times of signals; imaging is carried out once through the association calculation module (9) every time N times of signals are acquired;
Step 3, for single correlated imaging, a disclosed correlated imaging formula is adopted, and a second-order fluctuation correlated imaging formula is as follows:
Wherein G (x, y) is a single correlation imaging result, and x, y are two-dimensional image coordinates; n is the collection times; i i(x,y)、Bi is the ith reference light and object light signal in the N signals imaged at this time respectively; < I > and < B > are the average values of N reference light and object light signals imaged at this time, respectively;
And step 4, repeating the step 3 for M times to obtain M associated imaging results.
2. The associated imaging method based on high-speed modulated random medium doped optical fiber for abnormal cell screening in blood according to claim 1, wherein the wavelength of the laser source (1) is in the visible or infrared band.
3. The associated imaging method based on high-speed modulated random medium doped optical fiber for abnormal cell screening in blood according to claim 1, wherein the optical fiber coupling system (2) is a single lens or other device capable of coupling a laser source into an optical fiber.
4. A high-speed modulated random medium doped fiber based associated imaging method for screening abnormal cells in blood according to claim 1, wherein said fiber optic beam splitting system (5) is an optical device capable of splitting incident light into two beams of light with the same light field distribution.
5. A high-speed modulated random medium doped fiber based associative imaging method for screening abnormal cells in blood according to claim 1, wherein the multimode fiber (6-1) and the multimode fiber (6-2) are two identical multimode fibers, which are step index fibers, gradient index fibers or special fibers.
6. A high-speed modulated random medium doped fiber based associated imaging method for abnormal cell screening in blood according to claim 1, wherein said reference light acquisition system (7) comprises an imaging lens (7-1) and a CCD or CMOS device (7-2) with spatial resolution capability.
7. A high-speed modulated random medium doped fiber based associated imaging method for abnormal cell screening in blood according to 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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