Free activity state brain imaging system and method based on multimode fiber

Abstract

The invention provides a free activity state brain imaging system and method based on a multimode optical fiber, and belongs to the field of optical fiber brain imaging, the free activity state brain imaging system comprises a light source module, a modulation module, a multimode optical fiber probe, a correction module and a detection module; a multimode optical fiber is introduced to perform brain detection, a laser light source is modulated, a transmission focus point is generated at a transmission end of a multimode optical fiber probe, a reflection focus point is generated at a correction module, the bending state of the optical fiber probe is monitored in real time according to the intensity of the reflection focus point, and a currently used transmission matrix is adjusted in real time. And in combination with a fluorescence signal collected by the detection module, real-time brain imaging in a free activity state is realized. According to the invention, the introduced multimode optical fiber is small in diameter, high in resolution and small in damage to brain tissues, and more accurate, comprehensive and lossless research on the brain in a free activity state can be realized through real-time adjustment of an optical fiber transmission matrix.

Description

Technical Field

[0001] The present invention belongs to the field of fiber optic brain imaging, and particularly relates to a freely moving state brain imaging system and method based on multimode optical fibers. Background Art

[0002] In the field of neuroscience research, it is crucial to deeply explore brain functions and neural activities. Traditional brain imaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), etc., although have achieved remarkable results in the research of the brain in static or relatively fixed states, face many challenges when studying the brain activities of animals in freely moving states. fMRI devices are large in size and expensive, and the experimental subjects need to be in a strong magnetic field environment, which greatly limits their range of activities and cannot truly simulate the behaviors of animals in natural environments. PET involves the use of radioactive substances, which not only has strict requirements for the experimental environment and operation, but also is difficult to achieve continuous and long-term monitoring of animals in freely moving states.

[0003] In many neuroscience studies, such as studying the changes in brain nerve activities of animals during natural behaviors such as exploration, learning, and social interaction, a technology capable of performing high-resolution and real-time imaging of the brain in a freely moving state is required. Existing imaging devices and methods cannot meet this requirement, and there is an urgent need for a new technology to break through these limitations and achieve more accurate and comprehensive research on the brain in a freely moving state.

[0004] For example, the patent application with the publication number CN101828928A discloses a three-dimensional photoacoustic breast or cranial non-destructive imaging system, which mainly consists of a circular gear, an arc-shaped ultrasonic array, a bowl-shaped arc-shaped housing, an ultrasonic coupling liquid, a protective film, an optical path housing, a beam expander, an optical fiber, a laser, a data acquisition card, a preprocessing circuit, a stepper motor, a driver, a digital I / O card, a computer, and a display. The working process of the imaging system is as follows: the tissue to be measured generates photoacoustic signals under laser radiation, the arc-shaped ultrasonic array receives the photoacoustic signals and collects them into the computer; the driver drives the arc-shaped ultrasonic array to rotate around the tissue to be measured to the next position; repeat the steps of collection - rotation until enough photoacoustic signals at different positions are received, and the computer reconstructs the three-dimensional photoacoustic image of the tissue to be measured through calculation. Using the imaging system of the present invention, three-dimensional photoacoustic imaging of the breast or cranial cavity can be achieved quickly and non-destructively. Although this patent application can be used for photoacoustic analysis images of the brains of experimental animals in a freely moving state, there are quite large limitations in practical applications and it cannot achieve more accurate and comprehensive research on the brain in a freely moving state.

[0005] Multimode optical fiber is a highly potential imaging medium. Multimode optical fiber contains thousands of transmission modes within a diameter of the order of hundreds of micrometers and can transmit rich information. The imaging system based on multimode optical fiber has the advantages of small size, minimally invasive, and high resolution. By introducing multimode optical fiber, it is expected to achieve more accurate and comprehensive research on the brain in the freely moving state. Summary of the Invention

[0006] The object of the present invention is to provide a freely moving state brain imaging system and method based on multimode optical fiber. By introducing multimode optical fiber, in vivo brain imaging is performed on experimental animals, the light source is modulated, the transmission matrix of the optical fiber under different bending states is pre-calibrated, and during the actual imaging process, based on the intensity of the focal point at the reflection end of the optical fiber, the bending state of the optical fiber is monitored in real time, and the optical fiber transmission matrix is adjusted to achieve accurate, comprehensive and non-destructive research on the brain in the freely moving state.

[0007] To achieve the above object of the invention, an embodiment provides a freely moving state brain imaging system based on multimode optical fiber, including:

[0008] A light source module for emitting original light based on the light source;

[0009] A modulation module for modulating the original light emitted by the light source. The modulated light is coupled to the incident end of the multimode optical fiber probe, and after being transmitted through the optical fiber, transmitted light is formed at the transmission end respectively, and reflected light is formed at the correction module. Based on the transmitted light or the reflected light, the optical fiber transmission matrix reflecting the optical transmission characteristics of the optical fiber is calculated, and a transmitted focal point is formed at the transmission end, and a reflected focal point is formed at the correction module;

[0010] A multimode optical fiber probe for inserting into the brain and scanning the brain based on the transmitted focal point at the transmission end;

[0011] A correction module for monitoring the bending state of the multimode optical fiber probe in real time according to the intensity of the reflected focal point, and feeding back the reflected transmission matrix corresponding to the reflected focal point generating the maximum intensity to the modulation module to adjust the currently used optical fiber transmission matrix in real time;

[0012] A detection module for collecting the fluorescence signals excited by the transmitted focal point scanning the brain to achieve brain imaging in the freely moving state.

[0013] In one embodiment, a pre-calibrated optical fiber transmission matrix reflecting the optical fiber optical transmission characteristics is calibrated by a calibration module, and the calibration module includes: an objective lens, an imaging lens, a beam splitting prism, a collimating lens, and a high-speed camera, which are used to record an interference pattern by means of the high-speed camera under a certain optical fiber bending state, and then calculate the optical fiber transmission matrix based on the interference pattern, and change the optical fiber bending state to obtain a series of corresponding optical fiber transmission matrices; wherein the interference pattern is formed by the transmitted light emerging from the detection end of the multimode optical fiber passing through the objective lens and the imaging lens in sequence and then transmitted to the beam splitting prism, and the reference light separated by the light source passing through the single-mode optical fiber transmission and collimated by the collimating lens in sequence and interfering with the transmitted light at the beam splitting prism.

[0014] In one embodiment, calculating the optical fiber transmission matrix based on the interference pattern includes:

[0015] Under a certain optical fiber bending state, based on the interference pattern, solve the transmitted complex amplitude distribution and the reflected complex amplitude distribution of the optical fiber;

[0016] Taking the incident complex amplitude distribution of the optical fiber as the input and the transmitted complex amplitude distribution of the optical fiber as the output, establish a relationship to calculate the transmission transmission matrix; under the same bending state, taking the incident complex amplitude distribution of the optical fiber as the input and the reflected complex amplitude distribution of the optical fiber as the output, establish a relationship to calculate the reflection transmission matrix.

[0017] In one embodiment, the method for solving the transmitted complex amplitude distribution and the reflected complex amplitude distribution of the optical fiber includes: off-axis holography, intensity transmission equation or coaxial phase shift method.

[0018] In one embodiment, the multimode optical fiber probe is one of a quartz optical fiber, a plastic optical fiber, a glass optical fiber, and a photonic crystal optical fiber.

[0019] In one embodiment, the detection module is one of a high-speed camera, a photomultiplier tube, and an avalanche diode.

[0020] The present invention also provides a free-moving state brain imaging method based on a multimode optical fiber, using the free-moving state brain imaging system as described above, including the following steps:

[0021] Measure the transmission transmission matrix and the reflection transmission matrix of the multimode optical fiber, load a hologram on the spatial modulator of the modulation module by using the transmission transmission matrix to form a transmission focal point at the transmission end of the multimode optical fiber probe, and at the same time load a hologram on the spatial modulator of the modulation module by using the reflection transmission matrix to form a reflection focal point at the correction module;

[0022] Insert the multimode optical fiber probe into the brain, fix the position of the multimode optical fiber probe, perform point-by-point scanning through the transmission focal point at the transmission end of the multimode optical fiber probe to excite the fluorescence signal of the brain tissue, and the fluorescence signal is transmitted to the detection module through the optical path to reconstruct the brain imaging at the detection module;

[0023] Fix the contact surface between the multimode fiber optic probe and the skull in the observation area. When the animal is moving freely, monitor the bending state of the multimode fiber optic probe in real time according to the intensity change of the focal point at the reflection end, and adjust the currently used transmission matrix in real time according to the intensity of the focal point at the reflection end. Observe the brain imaging in the freely moving state in the detection module.

[0024] In one embodiment, before brain imaging in the freely moving state, it is necessary to obtain a pre-calibrated fiber optic transmission matrix that reflects the optical transmission characteristics of the fiber. The obtaining method includes: after the original light is collimated, it is divided into two paths of illumination light and reference light. The illumination light is incident on the modulation module, and after modulation, one of the paths is transmitted to the multimode fiber optic probe to form transmitted light. At the calibration module, the transmitted light and the reference light interfere to form an interference pattern, and the fiber optic transmission matrix is calculated based on the interference pattern. Change the fiber bending state and calculate the corresponding fiber optic transmission matrix and mapping relationship to obtain the pre-calibrated fiber optic transmission matrix in different bending states.

[0025] In one embodiment, the spatial modulator is one of a digital micromirror device, a liquid crystal spatial light modulator, and a deformable mirror.

[0026] Compared with the prior art, the beneficial effects of the present invention at least include:

[0027] (1) The fiber optic probe is based on a single multimode fiber, has a thin diameter, high resolution, and small damage to brain tissue;

[0028] (2) By introducing a modulation module, a calibration module, and a correction module, modulate the light source to generate a transmitted focal point and a reflected focal point. In the correction module, according to the intensity of the reflected focal point, combined with the pre-calibrated fiber optic transmission matrix, monitor the bending state of the fiber optic probe in real time to achieve more accurate research on the brain in the freely moving state. Description of the Drawings

[0029] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for the description of the embodiments or the prior art.

[0030] Figure 1 It is a schematic structural diagram of a freely moving state brain imaging system based on multimode fiber for actual imaging;

[0031] Figure 2 It is the head of a fiber optic probe provided in the embodiment;

[0032] Figure 3 It is a schematic structural diagram of a freely moving state brain imaging system based on multimode fiber before imaging;

[0033] Figure 4Schematic flowchart of a free - moving state brain imaging method based on multimode optical fiber provided for the embodiment. Detailed implementation manners

[0034] To make the objectives, technical solutions and advantages of the present invention clearer and more understandable, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific implementation manners described herein are only used to explain the present invention and do not limit the protection scope of the present invention.

[0035] To achieve a more accurate, comprehensive and non - destructive study of the brain in a free - moving state, as Figure 1 shown, as a preference of the specific implementation manner of the present invention, this embodiment provides a free - moving state brain imaging system based on multimode optical fiber. The system includes a light source module 1, a first collimating lens 2, a first beam - splitting prism 3, a modulation module 5, a calibration module 6, a single - mode optical fiber 7, a second objective lens 8, a multimode optical fiber probe 9, a first dichroic mirror 15, a second dichroic mirror 16, and a detection module 17.

[0036] The light source module 1 is used to emit original light based on the light source; the modulation module 5 is used to modulate the original light emitted by the light source. The modulated light is coupled to the incident end of the multimode optical fiber probe. After being transmitted through the optical fiber, transmitted light is formed at the transmission end and reflected light is formed at the calibration module. A fiber - optic transmission matrix reflecting the optical transmission characteristics of the optical fiber is calculated based on the transmitted light or the reflected light, and a transmitted focal point is formed at the transmission end and a reflected focal point is formed at the calibration module. The multimode optical fiber probe 9 is used to insert into the brain and scan the brain based on the transmitted focal point at the transmission end. The calibration module 6 is used to monitor the bending state of the multimode optical fiber probe in real time according to the intensity of the reflected focal point, and feedback the reflected transmission matrix corresponding to the reflected focal point with the maximum intensity to the modulation module to adjust the current fiber - optic transmission matrix used in real time. The detection module 17 is used to collect the fluorescence signals excited by the transmitted focal point scanning the brain, and realize brain imaging in a free - moving state.

[0037] As Figure 2 shown is a head of an optical fiber probe provided for the embodiment. 1 is a ceramic ferrule of the multimode optical fiber; 4 is a section of bare optical fiber, the length of which can be adjusted as needed, and a reflection slope can also be processed for side imaging; 3 is another ceramic ferrule used to fix the bare fiber; 2 is a ferrule sleeve used to fix 1 and 3, reduce the loss of the light source and the reflected fluorescence signals, and ensure sufficient coupling efficiency. The multimode optical fiber can be made of quartz optical fiber, plastic optical fiber, glass optical fiber, photonic crystal optical fiber, etc. The diameter and length of the optical fiber are determined by the size and depth of the field of view to be studied.

[0038] The spatial light modulation device in the modulation module can be selected from a series of devices that can freely control the optical wavefront, such as digital micromirror devices, liquid - crystal spatial light modulators, deformable mirrors, etc.

[0039] The detection module can be an optoelectronic detector such as a high-speed camera, a photomultiplier tube, an avalanche diode, etc.

[0040] Before imaging, as Figure 3 shown, the pre-calibrated optical fiber transmission matrix reflecting the optical fiber optical transmission characteristics is calibrated by a calibration module. The calibration module 18 includes: a third objective lens 10, an imaging lens 11, a second beam splitting prism 12, a second collimating lens 14, and a high-speed camera 13, which are used to record an interference pattern by the high-speed camera 13 in a state of an optical fiber bend, and then calculate the optical fiber transmission matrix based on the interference pattern, and change the optical fiber bend state to obtain a series of corresponding optical fiber transmission matrices; wherein the interference pattern is formed by the transmitted light emitted from the detection end of the multimode optical fiber passing through the third objective lens 10 and the imaging lens 11 in sequence and transmitted to the second beam splitting prism 12, and the reference light split from the light source interfering with the transmitted light at the second beam splitting prism 12 after passing through the single-mode optical fiber transmission and collimation by the second collimating lens 14 in sequence.

[0041] In the embodiment, calculating the optical fiber transmission matrix based on the interference pattern includes: in a state of an optical fiber bend, solving the transmitted complex amplitude distribution and the reflected complex amplitude distribution of the optical fiber based on the interference pattern;

[0042] Taking the optical fiber incident complex amplitude distribution as the input and the optical fiber transmitted complex amplitude distribution as the output, establishing a relationship to calculate the transmission transmission matrix; in the same bend state, taking the optical fiber incident complex amplitude distribution as the input and the optical fiber reflected complex amplitude distribution as the output, establishing a relationship to calculate the reflection transmission matrix.

[0043] Specifically, in a bend state, according to the interference pattern recorded by the high-speed camera 13, using off-axis holography, intensity transport equation or coaxial phase shift method to solve the transmitted light complex amplitude distribution and the reflected light complex amplitude distribution; taking the incident light complex amplitude distribution of the optical fiber as the input and the transmitted light complex amplitude distribution of the optical fiber as the output, establishing a relationship between the incident complex amplitude E i of the optical fiber and the transmitted light complex amplitude E o as E o = T t ·E i , and similarly establishing a relationship between the incident complex amplitude E i of the optical fiber and the reflected light complex amplitude E r as E r = T r ·E i , obtaining the corresponding transmission transmission matrix T t and reflection transmission matrix T r of the multimode optical fiber probe 9 in the current bend state.

[0044] Manually bend the optical fiber to different states within the activity range of the experimental animal, and repeat the above steps to obtain a series of transmission matrices and reflection matrices, completing the pre-calibration of the transmission matrices for multiple bending states of the optical fiber.

[0045] To clearly demonstrate the actual brain imaging process, for a free-moving state brain imaging system based on multimode optical fibers, this embodiment provides a free-moving state brain imaging method based on multimode optical fibers, as Figure 4 shown, including the following steps:

[0046] S1. Measure the transmission matrix and reflection matrix of the multimode optical fiber, use the transmission matrix to load a hologram on the spatial modulator of the modulation module to form a transmission focus point at the transmission end of the multimode optical fiber probe, and at the same time use the reflection matrix to load a hologram on the spatial modulator of the modulation module to form a reflection focus point at the correction module.

[0047] In the embodiment, insert the multimode optical fiber probe 9 into the brain of the experimental animal after anesthesia and craniotomy. Use the transmission matrix to load a hologram on the spatial light modulator in the modulation module 5 to modulate the excitation light source, and generate a scanning focus spot at the transmission end of the multimode optical fiber probe 9, which is the transmission end focus point; at the same time, load a hologram on the spatial light modulator through the reflection matrix, and the light reflected by the second dichroic mirror 16 is modulated by the spatial light modulator into a reflection focus point, which is recorded by the high-speed camera in the correction module 6 to form a focus spot, which is the reflection end focus point. The intensity of the reflection end focus point reflects the change in the bending state of the optical fiber. The stronger the intensity of the reflection end focus point, the closer the reflection matrix is to the current bending state of the optical fiber.

[0048] S2. Insert the multimode optical fiber probe into the brain, fix the position of the multimode optical fiber probe, and perform point-by-point scanning through the focus point at the transmission end of the multimode optical fiber probe to excite the fluorescence signal of the brain tissue. The fluorescence signal is transmitted through the optical path to the detection module, and the brain imaging is reconstructed in the detection module.

[0049] In the embodiment, use the transmission end focus point to scan and illuminate the position in front of the multimode optical fiber probe 9 to excite the fluorescence signal. The fluorescence is received by the same multimode optical fiber, and after passing through the second objective lens 8, the short-wave components of the excitation light are filtered by the first dichroic mirror 15 and the second dichroic mirror 16 in sequence, and only the long-wave fluorescence signal is retained. After entering the detection module 17, it is collected by the photodetector, and the light intensity information is recombined into an image according to the scanning order.

[0050] S3. Fix the contact surface between the multimode optical fiber probe and the skull in the observation area. When the animal is moving freely, monitor the bending state of the multimode optical fiber probe in real time according to the intensity change of the reflection end focus point, and adjust the currently used transmission matrix in real time according to the intensity of the reflection end focus point, and observe the brain imaging in the free-moving state in the detection module in real time.

[0051] In the embodiment, after finding the brain observation area of interest, the fiber optic probe is fixed to the head of the experimental animal with ultraviolet glue, biological tissue glue, and dental cement, so as to keep the observation area unchanged after the animal is awake and freely moving.

[0052] In actual imaging, the state of the transmission end is often unknown. In order to better achieve real-time brain imaging in the freely moving state, it is necessary to obtain the fiber optic transmission matrix under different pre-calibrated bending states before actual imaging.

[0053] Specifically, the transmitted light of the multimode fiber optic probe 9 is transmitted to the second beam splitter prism 12 through the third objective lens 10 and the imaging lens 11 in the calibration module 18. The original light emitted by the light source is split into a reference light by the first beam splitter prism 3, and then sequentially passes through the first objective lens 4 and the single-mode fiber 7 and is transmitted to the second beam splitter prism 12, where it interferes with the transmitted light of the multimode fiber optic probe 9 to form an interference pattern and is recorded by the high-speed camera 13. The fiber optic transmission matrix is calculated based on the interference pattern, and the corresponding fiber optic transmission matrix and mapping relationship are calculated by changing the fiber bending state.

[0054] Then, the bending state of the fiber optic probe is monitored in real time according to the intensity of the focal point at the reflection end of the fiber optic probe. By the focal point at the reflection end recorded in the correction module 6, a suitable transmission matrix is selected from a series of pre-calibrated fiber optic transmission matrices, and by predicting environmental changes, such as the approximate shape change path and temperature fluctuations, the corresponding transmission matrix is pre-calculated through actual measurement or simulation according to the corresponding physical parameters, and the pre-calibrated transmission matrix is compensated to make the intensity of the focal point at the reflection end the strongest. Then, the spatial light modulator is re-called to upload a new hologram to eliminate the influence caused by the fiber bending and achieve stable imaging of the fiber optic probe with the movement state of the experimental animal.

[0055] The above specific implementation manners have described in detail the technical solutions and beneficial effects of the present invention. It should be understood that the above is only the most preferred embodiment of the present invention and is not used to limit the present invention. Any modifications, supplements, equivalent replacements, etc. made within the principle scope of the present invention should be included within the protection scope of the present invention.

Claims

1. A free-motion brain imaging system based on multimode optical fiber, characterized in that: include: A light source module, used for emitting original light based on the light source; A modulation module is used to modulate the original light emitted by the light source, and the modulated light is coupled to the incident end of the multimode optical fiber probe. After being transmitted through the optical fiber, the light forms a transmitted light at the transmission end and a reflected light at the correction module. The optical fiber transmission matrix reflecting the optical transmission characteristics of the optical fiber is calculated based on the transmitted light or the reflected light, and a transmission focus point is formed at the transmission end, and a reflection focus point is formed at the correction module. A multimode optical fiber probe is used to be inserted into the brain to scan the brain based on the transmission focus point of the transmission end; The correction module is used to monitor the bending state of the multimode optical fiber probe in real time according to the intensity of the reflection focus point, and to feed back to the modulation module the current optical fiber transmission matrix used in real time based on the reflection transmission matrix corresponding to the reflection focus point with the maximum intensity; The detection module is used to collect the fluorescent signal stimulated by the transmission focus point when scanning the brain, so as to realize brain imaging in a free moving state.

2. The free-motion state brain imaging system according to claim 1, characterized in that: The pre-calibrated fiber transmission matrix reflecting the optical transmission characteristics of the fiber is calibrated through a calibration module, which includes: an objective lens, an imaging lens, a beam splitter, a collimating lens and a high-speed camera, and is used to record interference patterns using a high-speed camera in a fiber bending state, and then calculate the fiber transmission matrix based on the interference patterns, and change the fiber bending state to obtain a series of corresponding fiber transmission matrices; wherein the interference pattern is formed by transmitting the transmitted light emitted from the multi-mode fiber detection end through the objective lens and the imaging lens to the beam splitter in sequence, and the reference light separated from the light source is transmitted through the single-mode fiber and collimated by the collimating lens in sequence, and then interferes with the transmitted light at the beam splitter prism.

3. The free-motion state brain imaging system according to claim 2, characterized in that: Calculate the fiber transmission matrix based on the interference pattern, including: Under a fiber bending state, based on the interference pattern, the transmission complex amplitude distribution and reflection complex amplitude distribution of the fiber are solved; With the incident fiber complex amplitude distribution as input and the transmission fiber complex amplitude distribution as output, a relational expression is established to calculate the transmission transmission matrix; under the same bending state, with the incident fiber complex amplitude distribution as input and the reflection fiber complex amplitude distribution as output, a relational expression is established to calculate the reflection transmission matrix.

4. The free-motion state brain imaging system according to claim 3, characterized in that: Methods for solving the complex amplitude distribution of optical fiber transmission and reflection include: off-axis holography, intensity transmission equation or coaxial phase shift method.

5. The free-motion state brain imaging system according to claim 1, characterized in that: The multimode fiber probe is one of quartz fiber, plastic fiber, glass fiber, and photonic crystal fiber.

6. The free-motion state brain imaging system according to claim 1, characterized in that: The detection module is one of a high-speed camera, a photomultiplier tube, and an avalanche diode.

7. A method for free-motion brain imaging based on multimode optical fiber, characterized in that: Using the free-activity state brain imaging system according to any one of claims 1 to 6 comprises the following steps: The transmission transmission matrix and the reflection transmission matrix of the multimode optical fiber are measured, and a hologram is loaded on the spatial modulator of the modulation module using the transmission transmission matrix to form a transmission focal point at the transmission end of the multimode optical fiber probe. At the same time, a hologram is loaded on the spatial modulator of the modulation module using the reflection transmission matrix to form a reflection focal point at the correction module. Insert the multimode fiber probe into the brain, fix the position of the multimode fiber probe, scan point by point through the focusing point of the transmission end of the multimode fiber probe, stimulate the fluorescence signal of the brain tissue, transmit the fluorescence signal to the detection module through the optical path, and reconstruct the brain image in the detection module; The contact surface between the multimode fiber optic probe and the skull is fixed in the observation area. When the animal moves freely, the bending state of the multimode fiber optic probe is monitored in real time according to the intensity change of the focal point at the reflection end. The transmission matrix currently in use is adjusted in real time according to the intensity of the focal point at the reflection end. The brain imaging in the free movement state is observed in real time in the detection module.

8. The method for free-motion state brain imaging according to claim 7, characterized in that: Before brain imaging in a free-movement state, a pre-calibrated fiber transmission matrix that reflects the optical transmission characteristics of the fiber needs to be obtained. The method for obtaining the matrix includes: the original light is collimated and divided into two paths, namely, illumination light and reference light. The illumination light is incident on a modulation module, and one of the paths is transmitted to a multimode fiber probe after modulation to form a transmitted light. At the calibration module, the transmitted light interferes with the reference light to form an interference pattern. The fiber transmission matrix is ​​calculated based on the interference pattern. The corresponding fiber transmission matrix and mapping relationship are calculated by changing the fiber bending state, so as to obtain a pre-calibrated fiber transmission matrix under different bending states.

9. The method for free-motion state brain imaging according to claim 7, characterized in that: The spatial modulator is one of a digital micromirror device, a liquid crystal spatial light modulator, and a deformable mirror.

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