Four-mode synchronous imaging system and method based on chirped pulse amplification

Abstract

The invention relates to a four-mode synchronous imaging system and method based on chirped pulse amplification. The four-mode synchronous imaging system comprises a light source module, a photoacoustic light source broadening module, an optical coherence imaging module, a first light path conduction module, a high-speed scanning module, a second light path conduction module, an image acquisition module, a detection module and a photoacoustic signal processing module, and the light source module comprises a chirp amplification laser; the four-mode synchronous imaging system effectively realizes simultaneous detection of four imaging modes through a single parameter chirp amplification laser in combination with advanced optical and image processing technologies, improves the multi-dimensional information acquisition capability of imaging, simplifies the design of a multi-mode microscopic imaging system, reduces the complexity and cost of the system, and improves the detection efficiency. Meanwhile, the imaging efficiency and accuracy are improved, synchronous detection of various biological information can be achieved, and the method has wide application prospects, especially in the fields of medical pathology detection, neuroscience and the like.

Description

Technical Field

[0001] The present invention relates to the field of optical microscopy imaging technology, particularly multi-modal microscopy imaging technology, and more particularly to a four-modal synchronous imaging system and method based on chirped pulse amplification. Background Art

[0002] With the increasing demand for the study of cell and tissue microstructures in the biomedical field, microscopy imaging technology has become increasingly important in biomedical research. Although traditional single-modal microscopes have certain advantages in some aspects, they often cannot provide sufficient information when studying complex biological systems or multiple biological characteristics. Multi-modal microscopy imaging technology combines multiple imaging techniques and can simultaneously obtain the morphology, function, and physical properties of biological tissues, greatly improving the accuracy and integrity of imaging.

[0003] Existing multi-modal microscopy imaging systems often require different lasers to provide excitation light sources for each imaging modality respectively, which increases the complexity and cost of the system and limits the efficiency of real-time imaging. In addition, using multiple lasers as excitation for multiple modalities often results in imperfect fusion of imaging data between multiple modalities due to the intensity, phase, polarization direction, and pulse stability of the lasers. There are still technical bottlenecks in image calibration, alignment, and comprehensive processing of detection signals between various imaging modes.

[0004] Therefore, there is an urgent need for an innovative multi-modal microscopy imaging system that can meet the requirements of multiple imaging modalities under the drive of a single light source and perform unified detection and processing of multi-modal imaging results. Summary of the Invention

[0005] The object of the present invention is to address the problems existing in the prior art and propose a four-modal synchronous imaging system and method based on chirped pulse amplification.

[0006] The four-modal synchronous imaging system based on chirped pulse amplification provided by the embodiments of the present invention uses an optical parametric chirped pulse amplification laser to provide the excitation light sources required for different imaging modalities, greatly simplifying the system structure and reducing the equipment cost. Moreover, through the pulse compression and broadening technologies of the laser, the excitation requirements for multi-modal microscopy imaging are met. In addition, this system can simultaneously detect four-modal imaging and, through image processing algorithms, achieve efficient fusion of multi-modal images. Among them, the above four modalities include multi-photon microscopy (MPM), multi-harmonic microscopy (MHM), photoacoustic imaging (including photoacoustic microscopy, PAM, or photoacoustic computed tomography, PACT), and optical coherence imaging (including optical coherence microscopy, OCM, or optical coherence tomography, OCT). In the present invention, the images formed by these four modalities are fluorescence images, harmonic images, photoacoustic images, and optical coherence imaging images, respectively.

[0007] A detection method applying the four-modal synchronous imaging system based on chirped pulse amplification provided by the embodiments of the present invention has a micron-level spatial resolution and a millimeter-level imaging depth and is applicable to quantitative detection and diagnostic analysis of disease models such as cranial nerve imaging, glioma detection, lower limb ischemia, and diabetic foot. Through the four-modal synchronous imaging system and method based on chirped pulse amplification provided by the embodiments of the present invention, the imaging efficiency and accuracy of multi-modal microscopy imaging can be significantly improved, promoting the development of disease detection and scientific research, and having broad medical and scientific research application prospects.

[0008] To achieve the above object, in a first aspect, the embodiments of the present invention provide a four-modal synchronous imaging system based on chirped pulse amplification. The four-modal synchronous imaging system includes: a light source module, a photoacoustic light source broadening module, an optical coherence imaging module, a first optical path conduction module, a high-speed scanning module, a second optical path conduction module, an image acquisition module, a photoacoustic signal processing module, and a detection module; wherein, the light source module includes: a chirped amplification laser and an optical parametric amplification laser.

[0009] The laser emitted by the chirped amplification laser successively undergoes phase processing and beam splitting processing to form a first laser signal and a second laser signal; the optical parametric amplification laser performs chirped amplification processing on the first laser signal to form a chirped amplified laser signal; the photoacoustic light source broadening module broadens the second laser signal to generate a broadened laser signal; the optical coherence imaging module performs beam splitting processing on the chirped amplified laser signal to form a first amplified light signal and a second amplified light signal, and further reflects the first amplified light signal multiple times to form an interference reference light signal;

[0010] The broadened laser signal and the second amplified light signal are merged into the first optical path conduction module, and then successively pass through the first optical path conduction module, the high-speed scanning module, and the second optical path conduction module to enter the image acquisition module, exciting the sample to be measured in the image acquisition module to generate an ultrasonic signal and an excitation light signal respectively. The image acquisition module further separates the excitation light signal to generate a first sample light signal and a second sample light signal;

[0011] The photoacoustic signal processing module converts the ultrasonic electrical signal into a photoacoustic microscopy imaging electrical signal, and sends it to an external display device connected to the photoacoustic signal processing module to output a photoacoustic image;

[0012] The detection module separates the first sample light signal into a fluorescence signal and a harmonic signal, and detects them to generate a multi-photon imaging electrical signal and a multi-harmonic imaging electrical signal respectively, and sends them to an external display device connected to the detection module to output a fluorescence image and a harmonic image respectively;

[0013] The optical coherence imaging module performs beam combination interference processing on the second sample light signal and the interference reference light signal to generate an interference light signal, then performs photoelectric conversion processing on the interference light signal to generate an optical coherence imaging electrical signal, and sends the optical coherence imaging electrical signal to an external display device connected to the optical coherence imaging module to output an optical coherence imaging image.

[0014] Preferably, the light source module further includes: a first half-wave plate, a first polarization beam splitter prism, and a first mirror;

[0015] The laser emitted by the chirped amplification laser undergoes phase processing by the first half-wave plate and then beam splitting processing by the first polarization beam splitter prism to form a first laser signal and a second laser signal; the optical parametric amplification laser performs chirped amplification processing on the first laser signal to form a chirped amplified laser signal;

[0016] The second laser signal is reflected by the first mirror and enters the photoacoustic light source broadening module, and the photoacoustic light source broadening module broadens the second laser signal to generate a broadened laser signal;

[0017] The broadening process includes: grating dispersion pulse broadening or material dispersion pulse broadening;

[0018] When using the grating dispersion pulse broadening, the photoacoustic light source broadening module includes any one of a Martinez stretcher, an Offner stretcher, a Treacy stretcher, and a Martinez stretcher based on a 4F system;

[0019] When using the material dispersion pulse broadening, the broadening medium of the photoacoustic light source broadening module includes: quartz material or zinc selenide material.

[0020] Preferably, the optical coherence imaging module includes: a first beam splitting prism, an optical path compensation component, a second half-wave plate, a second polarization beam splitting prism, a quarter-wave plate, a silicon window plate, a beam combining prism, and an imaging component; wherein, the optical path compensation component includes: a retroreflecting prism and a plurality of plane mirrors; the retroreflecting prism moves according to the position of the sample to be measured; the imaging component includes: a first lens, an optical fiber, and a spectrometer; one end of the optical fiber is connected to the first lens, and the other end of the optical fiber is connected to the spectrometer;

[0021] The optical coherence imaging module splits the chirped amplified laser signal to form a first amplified optical signal and a second amplified optical signal, and further reflects the first amplified optical signal multiple times to form an interference reference optical signal, specifically including:

[0022] The first beam splitting prism splits the chirped amplified laser signal to form a first amplified optical signal and a second amplified optical signal; the plurality of plane mirrors reflect the first amplified optical signal to form a first reflected optical signal; the retroreflecting prism reflects the first reflected light to form an interference reference optical signal; wherein, the beam energy ratio of the first amplified optical signal to the second amplified optical signal is 1:99;

[0023] The second amplified optical signal sequentially passes through the second half-wave plate, the second polarization beam splitting prism, the quarter-wave plate, and then enters the first optical path conduction module after passing through the silicon window plate; the silicon window plate is placed at the Brewster angle to perform dispersion compensation on the second amplified optical signal;

[0024] The optical coherence imaging module combines the second sample optical signal and the interference reference optical signal for beam combination interference processing to generate an interference optical signal, then performs photoelectric conversion processing on the interference optical signal to generate an optical coherence imaging electrical signal, and sends the optical coherence imaging electrical signal to an external display device connected to the optical coherence imaging module to output an optical coherence imaging image, specifically including:

[0025] The second sample optical signal sequentially passes through the second optical path conduction module, the high-speed scanning module, and the first optical path conduction module and then returns to enter the optical coherence imaging module;

[0026] The beam combination prism combines the interference reference optical signal and the second sample optical signal for beam combination interference processing to form an interference optical signal; the first lens focuses the interference optical signal to form a focused imaging optical signal; the spectrometer obtains the focused imaging optical signal through the optical fiber and analyzes and processes the focused imaging optical signal to generate an optical coherence imaging electrical signal, and sends the optical coherence imaging electrical signal to an external display device connected to the spectrometer; the external display device processes the optical coherence imaging electrical signal to output an optical coherence imaging image.

[0027] Preferably, the broadened laser signal and the second amplified optical signal are merged into the first optical path conduction module, and then sequentially pass through the first optical path conduction module, the high-speed scanning module, and the second optical path conduction module to enter the image acquisition module, exciting the sample to be measured in the image acquisition module to respectively generate an ultrasonic signal and an excitation optical signal. The image acquisition module further separates the excitation optical signal to generate a first sample optical signal and a second sample optical signal, specifically including:

[0028] The broadened laser signal and the second amplified optical signal are merged into the first optical path conduction module, and are subjected to beam expansion, collimation, and reflection processing through the first optical path conduction module, so that the broadened laser signal forms a first incident optical signal and the second amplified optical signal forms a second incident optical signal;

[0029] The high-speed scanning module scans the first incident optical signal and the second incident optical signal, so that the first incident optical signal forms a first directional optical signal and the second incident optical signal forms a second directional optical signal;

[0030] The second optical path conduction module conducts the first directional optical signal and the second directional optical signal, so that the first directional optical signal and the second directional optical signal enter the image acquisition module;

[0031] The first directional optical signal excites the sample to be measured in the image acquisition module to generate an ultrasonic signal, and the ultrasonic signal is converted into an ultrasonic electrical signal by the image acquisition module and sent into the photoacoustic signal processing module; the second directional optical signal excites the sample to be measured to generate a sample excitation optical signal, and the sample excitation optical signal is separated by the image acquisition module to form a first sample optical signal and a second sample optical signal.

[0032] Further preferably, the first optical path conduction module includes: a first dichroic mirror, a plurality of lenses and a plurality of mirrors; the high-speed scanning module includes: one or more mirrors, a two-dimensional scanning device and a galvanometer;

[0033] The broadened laser signal is reflected by the first dichroic mirror and then undergoes beam expansion and collimation processing through the plurality of lenses and the plurality of mirrors in sequence to form the first incident optical signal; the second amplified optical signal passes through the first dichroic mirror and then undergoes beam expansion and collimation processing through the plurality of lenses and the plurality of mirrors in sequence to form the second incident optical signal; wherein, the first incident optical signal and the second incident optical signal are conducted in the same optical path;

[0034] The one or more mirrors adjust the incident angles of the first incident optical signal and the second incident optical signal; the two-dimensional scanning device scans the first incident optical signal and the second incident optical signal in the X-axis direction, and the galvanometer scans the first incident optical signal and the second incident optical signal in the Y-axis direction, so that the first incident optical signal forms a first directional optical signal and the second incident optical signal forms a second directional optical signal; the X-axis is perpendicular to the Y-axis; the second optical path conduction module includes a plurality of lenses and a plurality of mirrors for conducting the first directional optical signal and the second directional optical signal, so that the first directional optical signal and the second directional optical signal enter the image acquisition module; wherein, the first directional optical signal and the second directional optical signal are conducted in the same optical path.

[0035] Further preferably, the image acquisition module includes: a second dichroic mirror, an objective lens, an ultrasonic transducer and a water tank; wherein, the second dichroic mirror is placed above the objective lens; the ultrasonic transducer and the water tank are integrated on the objective lens; the ultrasonic transducer is annular and is placed on the lower surface of the objective lens or surrounds the side surface of the objective lens; the lower surface or the side surface of the objective lens and the ultrasonic transducer are immersed in the upper part of the water tank together; the sample to be measured is placed in the lower part of the water tank;

[0036] After the first directional optical signal and the second directional optical signal pass through the second dichroic mirror and enter the objective lens, they act on the sample to be measured;

[0037] The first directional optical signal excites the sample to be measured to generate an ultrasonic signal, and the ultrasonic transducer converts the ultrasonic signal into an ultrasonic electrical signal and sends it into the photoacoustic signal processing module; the second directional optical signal excites the sample to be measured to generate a sample excitation optical signal, and the second dichroic mirror separates the sample excitation optical signal to form a first sample optical signal and a second sample optical signal, so that the first sample optical signal is reflected into the detection module, and the second sample optical signal is transmitted into the second optical path conduction module.

[0038] Further preferably, the detection module includes: a third dichroic mirror, a multi-photon detection device and a multi-harmonic detection device; wherein, the multi-photon detection device includes a first photomultiplier tube; the multi-harmonic detection device includes a second photomultiplier tube;

[0039] The third dichroic mirror separates the first sample optical signal to form a fluorescence signal and a harmonic signal;

[0040] The first photomultiplier tube detects and analyzes the fluorescence signal to generate a multi-photon imaging electrical signal, and sends the multi-photon imaging electrical signal to an external display device connected to the first photomultiplier tube;

[0041] The second photomultiplier tube detects and analyzes the harmonic signal to generate a multi-harmonic imaging electrical signal, and sends the multi-harmonic imaging electrical signal to an external display device connected to the second photomultiplier tube.

[0042] Further preferably, the multi-photon detection device further includes a first band-pass filter; the multi-harmonic detection device includes a second band-pass filter;

[0043] The first band-pass filter is arranged between the third dichroic mirror and the first photomultiplier tube; the second band-pass filter is arranged between the third dichroic mirror and the second photomultiplier tube.

[0044] Preferably, the system further includes a main frame; the light source module, the photoacoustic light source broadening module, the optical coherence imaging module, the first optical path conduction module, the high-speed scanning module, the second optical path conduction module, the image acquisition module, the detection module and the photoacoustic signal processing module are arranged in the main frame;

[0045] The outside of the main frame has an opening for conducting signal lines and power supply lines to the outside world.

[0046] Second aspect, an embodiment of the present invention provides a method for applying the four-modal synchronous imaging system based on chirped pulse amplification described in the first aspect above. The four-modal synchronous imaging system based on chirped pulse amplification includes: a light source module, an optoacoustic light source broadening module, an optical coherence imaging module, a first optical path conduction module, a high-speed scanning module, a second optical path conduction module, an image acquisition module, an optoacoustic signal processing module, and a detection module; the light source module includes: a chirped amplification laser and an optical parametric amplification laser; the method includes:

[0047] The laser emitted by the chirped amplification laser undergoes phase processing by the first half-wave plate and then beam splitting processing by the first polarization beam splitter prism to generate a first laser signal and a second laser signal;

[0048] The optical parametric amplification laser acquires the first laser signal and forms a chirped amplified laser signal after chirped amplification processing;

[0049] The optoacoustic light source broadening module acquires the second laser signal and forms a broadened laser signal after broadening processing;

[0050] The optical coherence imaging module acquires the chirped amplified laser signal, undergoes beam splitting processing to generate a first amplified optical signal and a second amplified optical signal, and further reflects the first amplified optical signal multiple times to form an interference reference optical signal;

[0051] The first optical path conduction module sequentially performs beam expansion and collimation processing on the broadened laser signal and the second amplified optical signal, so that the broadened laser signal generates a first incident optical signal and the second amplified optical signal generates a second incident optical signal;

[0052] The high-speed scanning module acquires the first incident optical signal and the second incident optical signal, undergoes scanning processing, so that the first incident optical signal forms a first directional optical signal and the second incident optical signal forms a second directional optical signal;

[0053] The second optical path conduction module acquires the first directional optical signal and the second directional optical signal, and conducts the first directional optical signal and the second directional optical signal into the image acquisition module;

[0054] The image acquisition module acquires the first directional optical signal and the second directional optical signal. The first directional optical signal excites an ultrasonic signal in the sample to be measured in the image acquisition module, and the ultrasonic signal is converted into an ultrasonic electrical signal by the image acquisition module and sent to the optoacoustic signal processing module; the second directional optical signal excites a sample excitation optical signal in the sample to be measured, and the sample excitation optical signal is separated by the image acquisition module to form a first sample optical signal and a second sample optical signal;

[0055] The photoacoustic signal processing module collects the ultrasonic electrical signal, generates a photoacoustic microscopy imaging electrical signal through analysis and processing, and uses an external display device to process the photoacoustic microscopy imaging electrical signal to output a photoacoustic image;

[0056] The detection module acquires the first sample optical signal, forms a fluorescence signal and a harmonic signal through separation processing, detects the fluorescence signal to generate a multi-photon imaging electrical signal, and then sends the multi-photon imaging electrical signal to an external display device connected to the detection module, and uses the external display device to process the multi-photon imaging electrical signal to output a fluorescence image, and detects the harmonic signal to generate a multi-harmonic imaging electrical signal, and uses the external display device to process the multi-harmonic imaging electrical signal to output a harmonic image;

[0057] The optical coherence imaging module acquires the second sample optical signal, combines and interferes the second sample optical signal with the interference reference optical signal to generate an interference optical signal, and then performs photoelectric conversion processing on the interference optical signal to generate an optical coherence imaging electrical signal, and uses an external display device to process the optical coherence imaging electrical signal to output an optical coherence imaging image.

[0058] The four-modal synchronous imaging system based on chirped pulse amplification provided by the embodiments of the present invention uses an optical parametric chirped pulse amplification laser to provide the excitation light sources required for different imaging modalities, greatly simplifies the system structure, reduces the equipment cost, and meets the excitation requirements of multi-modal microscopy imaging through the pulse compression and broadening technologies of the laser. In addition, the system can simultaneously detect four-modal imaging, and through image processing algorithms, realizes the efficient fusion of multi-modal images.

[0059] A detection method applying the four-modal synchronous imaging system based on chirped pulse amplification provided by the embodiments of the present invention has a micron-level spatial resolution and a millimeter-level imaging depth, and is applicable to quantitative detection and diagnostic analysis of disease models such as cranial nerve imaging, glioma detection, lower limb ischemia, diabetic foot, etc.; through the four-modal synchronous imaging system and method based on chirped pulse amplification provided by the embodiments of the present invention, the imaging efficiency and accuracy of multi-modal microscopy imaging technology can be significantly improved, promoting the development of disease detection and scientific research, and having broad medical and scientific research application prospects.

[0060] The embodiments of the present invention provide a four-modal synchronous imaging system and method based on chirped pulse amplification, and the beneficial effects compared with the prior art are summarized as follows:

[0061] (1) Simplify the system structure: A single chirped pulse amplification laser is adopted, and the laser is separated, broadened, and compressed to enable it to output nanosecond pulses and femtosecond pulses simultaneously, so as to meet the requirements of photoacoustic microscopy imaging, multiphoton microscopy imaging, and multiple harmonic microscopy imaging respectively. At the same time, the excitation light source for multimodal microscopy imaging is unified, avoiding the complexity of a multi-laser system.

[0062] (2) Multimodal imaging fusion: The simultaneous detection of four imaging modalities is effectively achieved, improving the ability to obtain multi-dimensional information in imaging; moreover, the imaging depths, imaging characteristics, and resolutions of the four modalities are different. Through advanced image processing techniques, this four-modal synchronous imaging system can efficiently fuse and align the imaging results of the four modalities, ensuring the acquisition of imaging results of biological tissues with high spatial resolution, temporal resolution, and multi-dimensional information, achieving the effect of multi-modal fusion and complementarity.

[0063] (3) Adapt to a wide range of applications: The four-modal synchronous imaging system provided by the present invention can be applied to in-depth research of complex biological samples and real-time pathological detection, such as various application scenarios including cranial nerve imaging, glioma diagnosis, human and animal model detection, etc., with high flexibility and scalability. Brief Description of the Drawings

[0064] Figure 1 It is a structural block diagram of a four-modal synchronous imaging system based on chirped pulse amplification provided by an embodiment of the present invention.

[0065] Figure 2 It is a schematic structural diagram of three pulse stretcher models of grating dispersion pulse broadening provided by an embodiment of the present invention.

[0066] Figure 3 It is a schematic structural diagram of a Martinez stretcher based on a 4F system provided by an embodiment of the present invention.

[0067] Figure 4 It is a graph showing the change of dispersion characteristics of common optical materials calculated according to the Sellmeier equation for different materials provided by an embodiment of the present invention.

[0068] Figure 5 It is a second-order dispersion graph of the laser emitted by a chirped amplification laser with a central wavelength of 1030 nm provided by an embodiment of the present invention.

[0069] Figure 6 It is an example of a structure of a photoacoustic light source broadening module in a four-modal synchronous imaging system provided by an embodiment of the present invention.

[0070] Figure 7 It is another example of a structure of a photoacoustic light source broadening module in a four-modal synchronous imaging system provided by an embodiment of the present invention.

[0071] Figure 8 Schematic structural diagram of the four-modal synchronous imaging system based on chirped pulse amplification provided for Example 1. Specific embodiments

[0072] In order to make the objectives, technical solutions and advantages of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings. Obviously, the described embodiments are only a part rather than all of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0073] The technical solutions of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments.

[0074] Figure 1 It is a structural block diagram of a four-modal synchronous imaging system 1 based on chirped pulse amplification provided for an embodiment of the present invention, and the propagation path of light is also shown in Figure 1 as follows:

[0075] The four-modal synchronous imaging system 1 based on chirped pulse amplification includes: a light source module 11, a photoacoustic light source broadening module 12, an optical coherence imaging module 13, a first optical path conduction module 14, a high-speed scanning module 15, a second optical path conduction module 16, an image acquisition module 17, a photoacoustic signal processing module 18, and a detection module 19;

[0076] Among them, the light source module 11 includes: a chirped amplification laser 111 (CPA), an optical parametric amplification laser 112 (OPA), a first half-wave plate (not shown in the figure), a first polarization beam splitter prism (not shown in the figure), and a first reflector (not shown in the figure); the laser emitted by the chirped amplification laser is subjected to polarization processing by the first half-wave plate and then beam splitting processing by the first polarization beam splitter prism to form a first laser signal and a second laser signal; among them, optionally, the wavelength of the first laser signal is 1300 nm to 1700 nm; the wavelength of the second laser signal is 800 nm to 1064 nm. The optical parametric amplification laser 112 performs chirped amplification processing on the first laser signal to form a chirped amplification laser signal; preferably, the chirped amplification laser signal is a femtosecond pulse.

[0077] The photoacoustic light source broadening module 12 broadens the second laser signal that enters the photoacoustic light source broadening module 12 after being reflected by the first reflector to generate a broadened laser signal; preferably, the broadened laser signal is a nanosecond laser; among them, the broadening processing includes: grating dispersion pulse broadening or material dispersion pulse broadening. Specifically, when grating dispersion pulse broadening is adopted, the photoacoustic light source broadening module 12 includes but is not limited to: a Martinez stretcher, an Offner Any one of a stretcher, a Treacy stretcher, and a Martinez stretcher based on a 4F system; when material dispersion pulse broadening is adopted, the broadening medium of the photoacoustic light source broadening module 12 includes: a quartz material or a zinc selenide material.

[0078] The optical coherence imaging module 13 includes: a first beam splitting prism (not shown in the figure), an optical path compensation component 131, a second half-wave plate (not shown in the figure), a second polarization beam splitting prism (not shown in the figure), a quarter-wave plate (not shown in the figure), a silicon window (Silicon windows, not shown in the figure), a beam combining prism (not shown in the figure), and an imaging component 132; wherein, the optical path compensation component includes: a retroreflective prism and a plurality of plane mirrors; the retroreflective prism moves according to the position of the sample to be measured; the imaging component includes: a first lens, an optical fiber, and a spectrometer; one end of the optical fiber is connected to the first lens, and the other end of the optical fiber is connected to the spectrometer; the spectrometer includes, but is not limited to, a CCD spectrometer; wherein, the silicon window is placed at the Brewster angle to perform dispersion compensation on the second amplified optical signal, and thus a better three-modal imaging effect (including optical coherence imaging, fluorescence imaging, and harmonic imaging) can be obtained.

[0079] Specifically, the first beam splitting prism performs beam splitting on the chirped amplified laser signal to form a first amplified optical signal and a second amplified optical signal. Preferably, the beam energy ratio of the first amplified optical signal to the second amplified optical signal is 1:99. The plurality of plane mirrors reflect the first amplified optical signal to form a first reflected optical signal, and the retroreflective prism reflects the first reflected optical signal to form an interference reference optical signal. The second amplified optical signal passes through the second half-wave plate, the second polarization beam splitting prism, and the quarter-wave plate in sequence, and then enters the first optical path conduction module 14 after passing through the silicon window.

[0080] The first optical path conduction module 14 includes: a first dichroic mirror (not shown in the figure), a plurality of lenses (not shown in the figure), and a plurality of mirrors (not shown in the figure); the above-mentioned broadened laser signal is reflected by the first dichroic mirror, and then undergoes beam expansion and collimation processing by the plurality of lenses and the plurality of mirrors in sequence to form a first incident optical signal; the second amplified optical signal passes through the first dichroic mirror, and then undergoes beam expansion and collimation processing by the plurality of lenses and the plurality of mirrors in sequence to form a second incident optical signal. Among them, the conduction processes of the first incident optical signal and the first incident optical signal in the first optical path conduction module 14 are co-optical paths, that is, on the same light ray and physically basically coincident.

[0081] The high-speed scanning module 15 includes: one or more mirrors (not shown in the figure), a two-dimensional scanning device 151, and a galvanometer 152; among them, the two-dimensional scanning device 151 includes: one or more of a polygon scanning mirror, a MEMS scanning mirror, and an AOM scanning mirror. Specifically, one or more mirrors are used to adjust the incident angles of the first incident light signal and the second incident light signal, so that the first incident light signal and the second incident light signal enter the scanning ranges of the two-dimensional scanning device 151 and the galvanometer 152; the two-dimensional scanning device 151 scans the first incident light signal and the second incident light signal in the X-axis direction, and the galvanometer 152 scans the first incident light signal and the second incident light signal in the Y-axis direction, so that the first incident light signal forms a first directional light signal, and the second incident light signal forms a second directional light signal; where the X-axis is perpendicular to the Y-axis; the first directional light signal and the first directional light signal enter the second optical path conduction module 16 after being collimated by a lens.

[0082] The second optical path conduction module 16 includes a plurality of lenses (not shown in the figure) and a plurality of mirrors (not shown in the figure), and conducts the first directional light signal and the second directional light signal, so that the first directional light signal and the second directional light signal enter the image acquisition module 17. The conduction processes of the first directional light signal and the second directional light signal in the second optical path conduction module 14 are common optical paths, that is, on the same light ray and physically substantially coincident.

[0083] The image acquisition module 17 includes: a second dichroic mirror (not shown in the figure), an objective lens (not shown in the figure), an ultrasonic transducer (not shown in the figure), and a water tank (not shown in the figure); among them, the second dichroic mirror is placed above the objective lens, the ultrasonic transducer and the water tank are integrated on the objective lens, the ultrasonic transducer is annular, placed on the lower surface of the objective lens or surrounding the side surface of the objective lens, and will not block the laser signal emitted by the objective lens. At the same time, it can collect ultrasonic signals from the sample to be measured and convert the ultrasonic signals into ultrasonic electrical signals and conduct them to the photoacoustic signal processing module 18 for analysis and processing; the upper size of the water tank matches the objective lens, so that the lower surface of the objective lens and the ultrasonic transducer are completely immersed in the medium of the water tank, and the lower part of the water tank matches the sample, so that the sample can be completely immersed in water and ensure air isolation. Among them, the ultrasonic transducer of the present invention includes, but is not limited to, any one of a 64-array piezoelectric transducer, a 128-array piezoelectric transducer, and a 256-array piezoelectric transducer, and preferably a 256-array piezoelectric transducer. The medium contained in the water tank can be water or a coupling agent for ultrasonic detection

[0084] Specifically, after the first directional light signal and the second directional light signal pass through the second dichroic mirror and enter the objective lens, the first directional light signal excites the sample to be measured to generate ultrasonic signals, and the ultrasonic transducer converts the ultrasonic signals into ultrasonic electrical signals and sends them to the photoacoustic signal processing module 18, and the photoacoustic signal processing module 18 analyzes the ultrasonic electrical signals to generate photoacoustic images.

[0085] The second directional optical signal excites the sample to be measured to generate a sample excitation optical signal, and the sample excitation optical signal is separated by a second dichroic mirror to form a first sample optical signal and a second sample optical signal. The first sample optical signal is reflected into the detection module 19, and the second sample optical signal is transmitted into the second optical path conduction module 16.

[0086] The detection module 19 includes: a third dichroic mirror (not shown in the figure), a multi-photon detection device 191, and a multi-harmonic detection device 192. Among them, the multi-photon detection device 191 includes a first photomultiplier tube (not shown in the figure); the multi-harmonic detection device 192 includes a second photomultiplier tube (not shown in the figure). Specifically, the third dichroic mirror separates the above-mentioned first sample optical signal to form a fluorescence signal and a harmonic signal. The first photomultiplier tube detects and analyzes the fluorescence signal to generate a multi-photon imaging electrical signal, and sends the multi-photon imaging electrical signal to an external display device (not shown in the figure) connected to the first photomultiplier tube for outputting a fluorescence image. The second photomultiplier tube detects and analyzes the harmonic signal to generate a multi-harmonic imaging electrical signal, and sends the multi-harmonic imaging electrical signal to an external display device (not shown in the figure) connected to the second photomultiplier tube for outputting a harmonic image.

[0087] Optionally, the multi-photon detection device 191 further includes a first band-pass filter, and the first band-pass filter is disposed between the third dichroic mirror and the first photomultiplier tube; the multi-harmonic detection device 192 includes a second band-pass filter, and the second band-pass filter is disposed between the third dichroic mirror and the second photomultiplier tube.

[0088] The above-mentioned second sample optical signal sequentially passes through the second optical path conduction module 16, the high-speed scanning module 15, and the first optical path conduction module 14 and returns to the optical coherence imaging module 13.

[0089] The beam-combining prism in the optical coherence imaging module 13 performs beam-combining interference processing on the interference reference optical signal and the second sample optical signal to form an interference optical signal; the first lens focuses the interference optical signal to form a focused imaging optical signal; the spectrometer obtains the focused imaging optical signal through an optical fiber, analyzes and processes the focused imaging optical signal to generate an optical coherence imaging electrical signal, and sends the optical coherence imaging electrical signal to an external display device connected to the spectrometer to generate an optical coherence imaging.

[0090] In an alternative embodiment, the four-modal synchronous imaging system 1 based on chirped pulse amplification provided by the embodiments of the present invention further includes a main body frame (not shown in the figure); a light source module 11, an optoacoustic light source broadening module 12, an optical coherence imaging module 13, a first optical path conduction module 14, a high-speed scanning module 15, a second optical path conduction module 16, an image acquisition module 17, a detection module 19, and an optoacoustic signal processing module 18 are arranged inside the main body frame; there is an opening outside the main body frame for conducting signal lines and power supply lines to the outside world.

[0091] The embodiments of the present invention provide a detection method using the four-modal synchronous imaging system based on chirped pulse amplification in the first aspect above. The following is a description in conjunction with Figure 1 The detection method using the four-modal synchronous imaging system based on chirped pulse amplification will be described. The method specifically includes the following steps:

[0092] Step S1, start the light source module 11. The laser emitted by the chirped amplification laser passes through the polarization processing of the first half-wave plate and then through the beam splitting processing of the first polarization beam splitter prism to generate a first laser signal and a second laser signal.

[0093] Step S2, the optical parametric amplification laser 112 obtains the first laser signal and undergoes chirped amplification processing to form a chirped amplified laser signal.

[0094] Step S3, the optoacoustic light source broadening module 12 obtains the second laser signal and undergoes broadening processing to form a broadened laser signal.

[0095] Step S4, the optical coherence imaging module 13 obtains the chirped amplified laser signal, undergoes beam splitting processing to generate a first amplified optical signal and a second amplified optical signal, and further compensates the optical path for multiple reflections of the first amplified optical signal to form an interference reference optical signal.

[0096] Specifically, the first beam splitter prism in the optical coherence imaging module 13 performs beam splitting processing on the chirped amplified laser signal to form a first amplified optical signal and a second amplified optical signal; preferably, the beam energy ratio of the first amplified optical signal to the second amplified optical signal is 1:99; multiple plane mirrors perform reflection processing on the first amplified optical signal to form a first reflected optical signal; the retroreflective prism performs reflection processing on the first reflected light to form an interference reference optical signal. The second amplified optical signal passes through the second half-wave plate, the second polarization beam splitter prism, the quarter-wave plate in sequence, and then undergoes dispersion compensation through the silicon window plate before entering the first optical path conduction module 14.

[0097] Step S5: The first optical path conduction module 14 receives the broadened laser signal and the second amplified optical signal, and successively performs beam expansion and collimation processing on the broadened laser signal and the second amplified optical signal, so that the broadened laser signal generates a first incident optical signal, and the second amplified optical signal generates a second incident optical signal.

[0098] Specifically, the broadened laser signal is reflected by the first dichroic mirror in the first optical path conduction module 14, and then successively passes through the beam expansion and collimation processing of multiple lenses and multiple mirrors to form a first incident optical signal; the second amplified optical signal passes through the transmission of the first dichroic mirror, and then successively passes through the beam expansion and collimation processing of multiple lenses and multiple mirrors to form a second incident optical signal.

[0099] Step S6: The high-speed scanning module 15 acquires the first incident optical signal and the second incident optical signal, and through scanning processing, makes the first incident optical signal form a first directional optical signal, and makes the second incident optical signal form a second directional optical signal.

[0100] Specifically, the two-dimensional scanning device 151 in the high-speed scanning module 15 scans the first incident optical signal and the second incident optical signal in the X-axis direction, and the galvanometer 152 scans the first incident optical signal and the second incident optical signal in the Y-axis direction, so that the first incident optical signal forms a first directional optical signal, and the second incident optical signal forms a second directional optical signal; one or more mirrors in the high-speed scanning module 15 adjust the emission angles of the first directional optical signal and the first directional optical signal, so that the first directional optical signal and the first directional optical signal enter the second optical path conduction module 16.

[0101] Step S7: The second optical path conduction module 16 acquires the first directional optical signal and the second directional optical signal, and conducts the first directional optical signal and the second directional optical signal into the image acquisition module 17.

[0102] Specifically, the multiple lenses and multiple mirrors of the second optical path conduction module 16 conduct the first directional optical signal and the second directional optical signal, so that the first directional optical signal and the second directional optical signal enter the image acquisition module 17.

[0103] Step S8: The image acquisition module 17 acquires the first directional optical signal and the second directional optical signal. The first directional optical signal excites the sample to be measured in the image acquisition module 17 to generate an ultrasonic signal, and the ultrasonic signal is converted into an ultrasonic electrical signal by the image acquisition module 17 and sent to the photoacoustic signal processing module 18; the second directional optical signal excites the sample to be measured to generate a sample excitation optical signal, and the sample excitation optical signal is separated by the image acquisition module 17 to form a first sample optical signal and a second sample optical signal.

[0104] Specifically, the first and second directional optical signals acquired by the image acquisition module 17 pass through the second dichroic mirror, pass through the objective lens and act on the sample to be measured. The first directional optical signal excites the sample to be measured to generate an ultrasonic signal, and the ultrasonic transducer converts the ultrasonic signal into an ultrasonic electrical signal and sends it to the photoacoustic signal processing module 18. The photoacoustic signal processing module 18 analyzes the ultrasonic electrical signal to generate a photoacoustic image. The second directional optical signal excites the sample to be measured to generate a sample excitation optical signal, and the second dichroic mirror separates the sample excitation optical signal to form a first sample optical signal and a second sample optical signal, reflects the first sample optical signal into the detection module 19, and transmits the second sample optical signal into the second optical path conduction module 16.

[0105] Step S9: The photoacoustic signal processing module 18 collects the ultrasonic electrical signal, analyzes and processes it to generate a photoacoustic microscopy imaging electrical signal, and uses an external display device to process the photoacoustic microscopy imaging electrical signal to output a photoacoustic image.

[0106] Step S10: The detection module 19 acquires the first sample optical signal, separates and processes it to form a fluorescence signal and a harmonic signal, detects the fluorescence signal to generate a multi-photon imaging electrical signal, and then sends the multi-photon imaging electrical signal to an external display device connected to the detection module 19 for the external display device to process the multi-photon imaging electrical signal to output a fluorescence image, and detects the harmonic signal to generate a multi-harmonic imaging electrical signal for the external display device to process the multi-harmonic imaging electrical signal to output a harmonic image.

[0107] Specifically, the third dichroic mirror in the detection module 19 separates the first sample optical signal to form a fluorescence signal and a harmonic signal; the first photomultiplier tube detects and analyzes the fluorescence signal to generate a multi-photon imaging electrical signal, and sends the multi-photon imaging electrical signal to an external display device connected to the first photomultiplier tube to output a fluorescence image; the second photomultiplier tube detects and analyzes the harmonic signal to generate a multi-harmonic imaging electrical signal, and sends the multi-harmonic imaging electrical signal to an external display device connected to the second photomultiplier tube to output a harmonic image.

[0108] Step S11: The optical coherence imaging module 13 acquires the second sample optical signal, combines and interferes the second sample optical signal with an interference reference optical signal to generate an interference optical signal, and then performs photoelectric conversion processing on the interference optical signal to generate an optical coherence imaging electrical signal for an external display device to process the optical coherence imaging electrical signal to output an optical coherence imaging image.

[0109] Specifically, the beam combining prism in the optical coherence imaging module 13 combines the interference reference optical signal and the second sample optical signal for beam combining interference processing to form an interference optical signal; the first lens focuses the interference optical signal to form a focused imaging optical signal; the spectrometer acquires the focused imaging optical signal through an optical fiber, analyzes and processes the focused imaging optical signal, generates an optical coherence imaging electrical signal, and sends the optical coherence imaging electrical signal to an external display device connected to the spectrometer to output optical coherence imaging.

[0110] In the present invention, the parameters of the chirped pulse amplification laser (CPA) are not fixed and can be replaced according to different experimental requirements and imaging effect requirements. For example, the output parameters of the CPA can be set as: a laser with a central wavelength of 1030 nm, a full width at half maximum of 70 nm, and a pulse width of 200 fs; and then the laser emitted by the CPA is broadened into a picosecond pulse light source with a central wavelength of 1030 nm and a pulse width of 20 ps through the photoacoustic light source broadening module.

[0111] Laser broadening is to extend the time width of the laser pulse through different optical techniques, so that its spectral distribution is broader. The broadening processing methods in the present invention include: grating dispersion pulse broadening or material dispersion pulse broadening. When grating dispersion pulse broadening is adopted, the photoacoustic light source broadening module 12 includes, but is not limited to: any one of the Martinez stretcher, the Offner stretcher, the Treacy stretcher, and the Martinez stretcher based on the 4F system; when material dispersion pulse broadening is adopted, the broadening medium of the photoacoustic light source broadening module 12 includes: quartz material or zinc selenide material. The following will respectively describe different types of broadening methods. The broadening medium of the photoacoustic light source broadening module 12 includes: quartz material or zinc selenide material. The following will respectively describe different types of broadening methods.

[0112] Figure 2 FIG. 12 is a schematic structural diagram of three pulse stretcher models for grating dispersion pulse broadening provided by an embodiment of the present invention, where Figure 2 A is a schematic diagram of the Offner stretcher, which is composed of a grating, a concave mirror, a convex mirror, and a plane mirror. The specific size of the stretcher and the grating size can be customized; Figure 2 B is a schematic diagram of the Martinez type stretcher, which is composed of a grating, a concave mirror, and a plane mirror; Figure 3 C is a schematic diagram of the Treacy stretcher, which is composed of a pair of gratings arranged in parallel.

[0113] Figure 3 FIG. 22 is a schematic structural diagram of another Martinez stretcher based on the 4F system provided by an embodiment of the present invention. This structure is composed of a pair of gratings, a pair of coupled lenses, and two mirrors.

[0114] The broadening amount of the Martinez stretcher based on the 4F system is calculated by the following formula:

[0115] For this structure:

[0116] First-order dispersion

[0117] Second-order dispersion

[0118] Third-order dispersion

[0119] where L g is the grating pair spacing, γ is the grating incident angle, θ is the diffraction angle, d is the distance between the two gratings, λ is the wavelength of the laser, the wavelength used in the present invention is 1030 nm, and c is the speed of light.

[0120] Since the first-order dispersion usually translates the overall phase of the laser and does not affect the components related to the frequency, this term does not need to be considered in the pulse broadening. The second-order dispersion is usually the main factor causing pulse broadening. The third-order dispersion usually has a much smaller effect than the second-order dispersion and is difficult to exist independently of the second-order dispersion. Therefore, only the second-order dispersion is considered when broadening the pulse width with the grating pair.

[0121] From the pulse broadening formula:

[0122] where τ out represents the target broadened pulse width, τ in represents the input laser pulse width, represents the second-order dispersion. For the central wavelength of 1030 nm used in this patent, when a 200 fs laser is broadened to 20 ps, substituting into the calculation gives the required second-order dispersion amount as: 1442622.90 fs 2 , so substituting the second-order dispersion into the above formula can specifically customize the specific parameters of the grating pair required for this patent for use in the pulse stretcher of the present invention.

[0123] Figure 4 is the dispersion characteristic of common optical materials calculated according to the Sellmeier equation for different materials, where Figure 4 A represents the variation diagram of the refractive index of different materials with the wavelength, Figure 4 B represents the variation diagram of the second-order group velocity dispersion (GVD) of different materials with the wavelength, Figure 4 C represents the variation diagram of the third-order dispersion (TOD) of different materials with the wavelength, Figure 4 D represents the Abbe number of different materials, representing the degree of change in their dispersion.

[0124] Due to the diffraction grading of the grating, usually only the energy from the zero-order to the first-order can be utilized in the grating broadening structure, resulting in a relatively low energy utilization rate of the grating broadening structure, and a lot of energy is wasted. Therefore, it is preferable to use the second-order dispersion characteristic of the material itself for pulse broadening.

[0125] Figure 5 It is the second-order dispersion diagram of the chirped amplifier laser with a central wavelength of 1030 nm provided by the embodiment of the present invention. It can be seen that in the detailed diagrams of the variation of the second-order group velocity dispersion (GVD) of different materials with wavelength, the red dashed line represents the position of the central wavelength of the chirped amplifier laser used in the present invention, and the yellow boxed area is the spectral bandwidth coverage area of the chirped amplifier laser used in the present invention. There are three materials in the yellow boxed area that satisfy the second-order group velocity dispersion greater than 0 and with obvious changes: zinc selenide (ZnSe), titanium sapphire crystal (Ti:Sapphire), and fused silica material (Fused Silicon). Since the titanium sapphire material is expensive and difficult to process, the present invention preferably selects two materials, zinc selenide and fused silica material, as the dispersion material substrate of the above-mentioned photoacoustic light source broadening module 12.

[0126] Through calculation, the second-order dispersions of the two materials are as follows: the second-order dispersion GVD of the zinc selenide material at 1030 nm = 724.75 fs 2 / mm, and the second-order dispersion GVD of the fused silica material at 1030 nm = 203.00 fs 2 / mm; Similarly, through the formula, it is calculated that for a laser with a central wavelength of 1030 nm and a pulse width of 200 fs to be broadened to 20 ps, the second-order dispersion amount GDD to be compensated = 1442622.90 fs 2 Therefore, if the fused silica material is used for compensation, the required length is 7106.52 mm, and if the zinc selenide material is used for compensation, the required material length is 1990.51 mm.

[0127] Figure 6This is an example of the structure of an optical-acoustic light source broadening module in a four-modal synchronous imaging system provided by an embodiment of the present invention. By adjusting the reflection angle of the mirror group, the optical path of the laser passing through the quartz material or zinc selenide material is adjusted, and the second-order dispersion is used to broaden the laser pulse. The figure includes the top view, perspective view, and side view of the optical-acoustic light source broadening module. Taking the top view as an example, the incident light enters the silicon-based glass rod from the lower left corner and passes through the mirror group (a mirror group composed of 6 mirrors in the figure, and the number and angle of the mirrors are adjusted according to the actual situation) multiple times in the silicon-based glass rod and exits from the upper right corner. The number of times the laser passes through the silicon-based glass rod is proportional to the optical path it passes through, and the optical path it passes through is proportional to the pulse broadening amount. By adjusting the number of passes, the purpose of controlling the laser pulse broadening is achieved, and thus the femtosecond laser is broadened into a nanosecond laser.

[0128] It should be noted that Figure 6 The six groups of mirror structures shown are only for demonstration purposes, and different mirror structures can be added or adjusted according to the magnitude of the dispersion to be adjusted in actual use. Figure 6 The six groups of mirror structures shown have the advantages of simple structure and convenient adjustment, and support fine-tuning of the dispersion compensation amount. However, energy loss is likely to occur when entering and exiting the dispersion material and the air surface.

[0129] Such as Figure 7 As shown, it is another dispersion compensation structure based on total internal reflection. By using the phenomenon of total internal reflection of the laser on the inner surface of the material, the effects of reducing energy loss and maintaining polarization characteristics are achieved. The total internal reflection phenomenon occurs when light travels from an optically denser medium (a medium with a larger refractive index) to an optically thinner medium (a medium with a smaller refractive index). When the incident angle is greater than a certain critical angle, the light will not enter the second medium but will be completely reflected back into the first medium, resulting in the total internal reflection phenomenon. At this time, the energy loss can be ignored. The formula for calculating the total internal reflection angle is:

[0130] Figure 7 This is another example of the structure of an optical-acoustic light source broadening module in a four-modal synchronous imaging system provided by an embodiment of the present invention. The optical-acoustic light source broadening module uses the total internal reflection structure to improve the laser energy utilization efficiency. In the figure, the red arrow is the laser passing path, the blue filling is the dispersion material substrate, and the blue triangular shape is a customized optical window for laser incidence and exit.

[0131] Among them, Figure 7 A is a rectangular total internal reflection dispersion material structure. The incident light is obliquely incident from the upper customized window, undergoes multiple total internal reflections on the inner surface of the dispersion material substrate, and finally exits obliquely from the upper surface window. The length of the dispersion material is L, the width is S, and the total internal reflection angle is φ. Then the total optical path passed through in the material is: Among them, L needs to satisfy: is an integer. This optical path is the effective broadening optical path of the dispersion broadening material.

[0132] Figure 7 B is a total internal reflection structure based on an N-sided polygon, where the incident light enters from the left window, undergoes total internal reflection on the inner surface of the centers of the sides of the N-sided polygon, and exits from the left window after cycling once. The number of sides of the N-sided polygon dispersion material is N, the inscribed circle radius is R, the side length is T, and the total internal reflection angle is γ. Then the total optical path passed through in the material is: Among them, the relationship between the total internal reflection angle γ and the number of sides N needs to satisfy: By adjusting the number of sides of the N-sided polygon, the requirements for the total internal reflection angle of different materials can be met, and by adjusting the side length, the dispersion amount can be controlled.

[0133] The advantages of the above two structures are as follows. First, through total internal reflection, the loss of light energy is reduced. Second, by calculating specific reflection angles, as well as customized incident and exit windows and the reflection occurrence points, the optical path and path of light passing through the material can be precisely controlled, which is convenient for calculation, observation, and adjustment. Compared with the structure using mirrors, where adjusting one mirror may require continuous adjustment of other subsequent mirrors, the convenience of this structure is greatly improved.

[0134] The windows of these two structures are customized Brewster angle incident windows, which can reduce the energy loss from the air medium to the dispersion medium substrate. The formula for calculating the Brewster angle is: Among them, θ B is the Brewster angle, and n1 and n2 are the refractive indices of the two media respectively. After calculation, the Brewster angle between the zinc selenide material and the air surface is: 67.93 degrees; the Brewster angle between the fused silica material and the air surface is: 55.87 degrees.

[0135] To better understand the technical solution provided by the present invention, the following uses specific examples to illustrate the four-mode synchronous imaging system based on chirped pulse amplification of the present invention and the method for detecting using this system.

[0136] Example 1

[0137] The embodiment of the present invention provides a four-mode synchronous imaging system based on chirped pulse amplification. As Figure 8 shown in the structural schematic diagram, the structural composition of the four-mode synchronous imaging system 2 based on chirped pulse amplification includes: a light source module a, a photoacoustic light source broadening module b, an optical coherence imaging module c, a first optical path conduction module d, a high-speed scanning module e, a second optical path conduction module f, an image acquisition module g, a photoacoustic signal processing module m, and a detection module n.

[0138] Among them, the light source module a includes: a chirped pulse amplification laser (CPA), an optical parametric amplification laser (OPA), a half-wave plate 20, a polarization beam splitter prism 21, and a mirror 22.

[0139] The photoacoustic light source broadening module b adopts the structure as Figure 6 shown, and adjusts the optical path of the laser passing through the zinc selenide material by adjusting the reflection angle of the mirror group, and uses the second-order dispersion to broaden the laser pulse.

[0140] The optical coherence imaging module c includes: a beam splitter prism 23, a retroreflective prism 24, multiple plane mirrors 25, a half-wave plate 26, a polarization beam splitter prism 27, a quarter-wave plate 28, a silicon window plate 29, a beam combining prism 30, a lens 31, an optical fiber 32, and a CCD spectrometer 33.

[0141] The first optical path conduction module d includes: a dichroic mirror 34, a lens 35, a lens 36, and a mirror 37.

[0142] The high-speed scanning module e includes: a mirror 38, a two-dimensional scanning device 39, and a galvanometer 40.

[0143] The second optical path conduction module f includes: a lens 41, a mirror 42, a lens 43, and a mirror 44.

[0144] The image acquisition module g includes: a dichroic mirror 45, an objective lens 46, an ultrasonic transducer (not shown in the figure), and a water tank 47; among them, the ultrasonic transducer and the water tank 47 are integrated on the objective lens, the ultrasonic transducer is annular and placed on the side surface of the objective lens 46, the side surface of the objective lens 46 is immersed in the upper part of the water tank 47, and the sample to be measured is placed in the lower part of the water tank 47.

[0145] The detection module n includes: a lens 48, a dichroic mirror 49, a photomultiplier tube 50, and a photomultiplier tube 51.

[0146] The detection method using the four-modal synchronous imaging system 2 based on chirped pulse amplification in Embodiment 1 is specifically as follows:

[0147] (1) Start the light source module a. The laser emitted by the chirped pulse amplification laser (CPA) undergoes polarization processing by the half-wave plate 20, and then undergoes beam splitting processing by the polarization beam splitter prism 21 to generate a first laser signal and a second laser signal. The first laser signal enters the optical parametric amplification laser (OPA), and the second laser signal is reflected by the mirror 22 and enters the photoacoustic light source broadening module b. Among them, the laser wavelength is 1030 nm.

[0148] (2) The optical parametric amplification laser (OPA) obtains the first laser signal and undergoes chirped pulse amplification processing to form a chirped pulse amplified laser signal.

[0149] (3) The photoacoustic light source broadening module b obtains a second laser signal, which is broadened to form a broadened laser signal.

[0150] (4) The beam splitting prism 23 in the optical coherence imaging module c splits the chirped amplified laser signal to form a first amplified optical signal and a second amplified optical signal with a beam energy ratio of 1:99.

[0151] Multiple plane mirrors 25 perform multiple reflection processes on the first amplified optical signal, and finally form a reflected optical signal. The retroreflective prism 24 reflects the reflected light to form an interference reference optical signal.

[0152] The second amplified optical signal passes through a half-wave plate 26, a polarization beam splitting prism 27, a quarter-wave plate 28 in sequence, and after dispersion compensation through a silicon window plate 29, it enters the first optical path conduction module d.

[0153] (5) The broadened laser signal is reflected by the dichroic mirror 34 in the first optical path conduction module d, and then undergoes beam expansion and collimation processing through a lens 35, a lens 36, and a mirror 37 in sequence to form a first incident optical signal. The second amplified optical signal passes through the dichroic mirror 34 by transmission, and then undergoes beam expansion and collimation processing through a lens 35, a lens 36, and a mirror 37 in sequence to form a second incident optical signal.

[0154] (6) The mirror 38 in the high-speed scanning module e adjusts the incident angles of the first incident optical signal and the second incident optical signal, so that the first incident optical signal and the second incident optical signal enter the two-dimensional scanning device 39 and the galvanometer 40 for scanning. Among them, the two-dimensional scanning device 39 scans the first incident optical signal and the second incident optical signal in the X-axis direction, and the galvanometer 40 scans the first incident optical signal and the second incident optical signal in the Y-axis direction, so that the first incident optical signal forms a first directional optical signal, and the second incident optical signal forms a second directional optical signal.

[0155] (7) The lens 41, the mirror 42, the lens 43, and the mirror 44 in the second optical path conduction module f conduct the first directional optical signal and the second directional optical signal, so that the first directional optical signal and the second directional optical signal enter the image acquisition module g.

[0156] (8) The first directional optical signal and the second directional optical signal obtained by the image acquisition module g pass through the dichroic mirror 45, and then pass through the objective lens 46 and act on the sample to be measured. The first directional optical signal excites the sample to be measured to generate an ultrasonic signal, and the ultrasonic signal is converted into an ultrasonic electrical signal by an ultrasonic transducer (not shown in the figure) and sent to the photoacoustic signal processing module m. The photoacoustic signal processing module m collects the ultrasonic electrical signal, analyzes and processes it to generate a photoacoustic microscopy imaging electrical signal, and uses an external display device to process the photoacoustic microscopy imaging electrical signal to output a photoacoustic image.

[0157] The second directional optical signal excites the sample to be measured to generate a sample excitation optical signal, and the dichroic mirror 45 separates the sample excitation optical signal to form a first sample optical signal and a second sample optical signal, so that the first sample optical signal is reflected into the detection module n, and the second sample optical signal is transmitted into the second optical path conduction module f.

[0158] (9) The lens 48 in the detection module n collimates the first sample optical signal, and the dichroic mirror 49 separates the collimated first sample optical signal to form a fluorescence signal and a harmonic signal.

[0159] The photomultiplier tube 50 detects and analyzes the fluorescence signal, generates a multi - photon imaging electrical signal, and sends the multi - photon imaging electrical signal to an external display device connected to the photomultiplier tube 50 for outputting a fluorescence image.

[0160] The photomultiplier tube 51 detects and analyzes the harmonic signal, generates a multi - harmonic imaging electrical signal, and sends the multi - harmonic imaging electrical signal to an external display device connected to the photomultiplier tube 51 for outputting a harmonic image.

[0161] (10) The second sample optical signal passes through the second optical path conduction module f, the high - speed scanning module e, and the first optical path conduction module d in sequence and returns to the optical coherence imaging module c; the beam - combining prism 30 performs beam - combining interference processing on the interference reference optical signal and the second sample optical signal to form an interference optical signal; the lens 31 focuses the interference optical signal to form a focused imaging optical signal; the CCD spectrometer 33 obtains the focused imaging optical signal through the optical fiber 32, analyzes and processes the focused imaging optical signal, generates an optical coherence imaging electrical signal, and sends the optical coherence imaging electrical signal to an external display device connected to the CCD spectrometer 33 for outputting an optical coherence imaging.

[0162] Those skilled in the art should further realize that the units and algorithm steps of each example described in combination with the embodiments disclosed in this article can be implemented by electronic hardware, computer software, or a combination of the two. To clearly illustrate the interchangeability of hardware and software, the composition and steps of each example have been generally described according to functions in the above description. Whether these functions are executed in a hardware or software manner depends on the specific application and design constraints of the technical solution. Skilled professionals can use different methods for each specific application to implement the described functions, but such implementation should not be considered to exceed the scope of the present invention.

[0163] The steps of the methods or algorithms described in connection with the embodiments disclosed herein may be implemented in hardware, software modules executed by a processor, or a combination of both. The software modules may be placed in a random access memory (RAM), memory, read-only memory (ROM), electrically programmable ROM, electrically erasable programmable ROM, registers, hard disk, removable disk, CD-ROM, or any other form of storage medium known in the art.

[0164] The specific embodiments described above have further elaborated on the object, technical solution, and beneficial effects of the present invention. It should be understood that the above description is only for the specific embodiments of the present invention and is not used to limit the protection scope of the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A four-modal synchronous imaging system based on chirped pulse amplification, characterized in that: The four-modal synchronous imaging system includes: a light source module, a photoacoustic light source broadening module, an optical coherence imaging module, a first light path transmission module, a high-speed scanning module, a second light path transmission module, an image acquisition module, a photoacoustic signal processing module and a detection module; wherein the light source module includes: a chirped amplification laser and an optical parametric amplification laser; The laser emitted by the chirped amplified laser is subjected to phase processing and beam splitting processing in sequence to form a first laser signal and a second laser signal; the optical parametric amplifier laser performs chirp amplification processing on the first laser signal to form a chirped amplified laser signal; the photoacoustic light source widening module performs widening processing on the second laser signal to generate a widened laser signal; the optical coherence imaging module performs beam splitting processing on the chirped amplified laser signal to form a first amplified light signal and a second amplified light signal, and further reflects the first amplified light signal multiple times to form an interference reference light signal; The broadened laser signal and the second amplified optical signal are merged into the first optical path transmission module, and then sequentially pass through the first optical path transmission module, the high-speed scanning module, and the second optical path transmission module to enter the image acquisition module, and excite the sample to be tested in the image acquisition module to generate an ultrasonic signal and an excitation optical signal respectively. The image acquisition module further separates the excitation optical signal to generate a first sample optical signal and a second sample optical signal; The photoacoustic signal processing module converts the ultrasonic electrical signal into a photoacoustic microscopy imaging electrical signal, sends the signal to an external display device connected to the photoacoustic signal processing module, and outputs a photoacoustic image; The detection module separates the first sample light signal into a fluorescence signal and a harmonic wave signal, detects the first sample light signal and generates a multi-photon imaging electrical signal and a multi-harmonic imaging electrical signal, respectively, sends the signals to an external display device connected to the detection module, and outputs a fluorescence image and a harmonic wave image respectively; The optical coherence imaging module performs beam combining interference processing on the second sample light signal and the interference reference light signal to generate an interference light signal, then performs photoelectric conversion processing on the interference light signal to generate an optical coherence imaging electrical signal, and sends the optical coherence imaging electrical signal to an external display device connected to the optical coherence imaging module to output an optical coherence imaging image.

2. The four-modality synchronous imaging system based on chirped pulse amplification according to claim 1, characterized in that: The light source module further includes: a first half-wave plate, a first polarization beam splitter prism and a first reflector; The laser emitted by the chirped amplified laser is subjected to phase processing by the first half-wave plate and then to beam splitting processing by the first polarization beam splitter prism to form a first laser signal and a second laser signal; the optical parametric amplifier laser performs chirp amplification processing on the first laser signal to form a chirped amplified laser signal; The second laser signal is reflected by the first reflector and enters the photoacoustic light source widening module, and the photoacoustic light source widening module performs widening processing on the second laser signal to generate a widened laser signal; The broadening process includes: grating dispersion pulse broadening or material dispersion pulse broadening; When the grating dispersion pulse stretching is adopted, the photoacoustic light source stretching module includes: any one of a Martinez stretcher, an Oeffler stretcher, a Trichy stretcher, and a Martinez stretcher based on a 4F system; When material dispersion pulse broadening is adopted, the broadening medium of the photoacoustic light source broadening module includes: quartz material or zinc selenide material.

3. The four-modality synchronous imaging system based on chirped pulse amplification according to claim 1, characterized in that: The optical coherence imaging module comprises: a first beam splitter prism, an optical path compensation component, a second half-wave plate, a second polarization beam splitter prism, a quarter-wave plate, a silicon window plate, a beam combining prism and an imaging component; wherein the optical path compensation component comprises: a retroreflective prism and a plurality of plane reflectors; the retroreflective prism moves according to the position of the sample to be measured; the imaging component comprises: a first lens, an optical fiber and a spectrometer; one end of the optical fiber is connected to the first lens, and the other end of the optical fiber is connected to the spectrometer; The optical coherent imaging module performs beam splitting processing on the chirped amplified laser signal to form a first amplified optical signal and a second amplified optical signal, and further reflects the first amplified optical signal multiple times to form an interference reference optical signal, specifically including: The first beam splitter performs beam splitting processing on the chirped amplified laser signal to form a first amplified light signal and a second amplified light signal; the plurality of plane reflectors perform reflection processing on the first amplified light signal to form a first reflected light signal; the retroreflective prism performs reflection processing on the first reflected light to form an interference reference light signal; wherein the beam energy ratio between the first amplified light signal and the second amplified light signal is 1:99; The second amplified optical signal sequentially passes through the second half-wave plate, the second polarization beam splitter prism, the quarter-wave plate, and then passes through the silicon window plate, and then enters the first optical path transmission module; the silicon window plate is placed according to the Brewster angle to perform dispersion compensation on the second amplified optical signal; The optical coherence imaging module performs beam combining interference processing on the second sample light signal and the interference reference light signal to generate an interference light signal, then performs photoelectric conversion processing on the interference light signal to generate an optical coherence imaging electrical signal, and sends the optical coherence imaging electrical signal to an external display device connected to the optical coherence imaging module to output an optical coherence imaging image, specifically including: The second sample light signal passes through the second light path transmission module, the high-speed scanning module, and the first light path transmission module in sequence and returns to the optical coherence imaging module; The beam combining prism combines the interference reference light signal and the second sample light signal to form an interference light signal; the first lens focuses the interference light signal to form a focused imaging light signal; the spectrometer acquires the focused imaging light signal through the optical fiber, analyzes and processes the focused imaging light signal to generate an optical coherence imaging electrical signal, and sends the optical coherence imaging electrical signal to an external display device connected to the spectrometer; the external display device processes the optical coherence imaging electrical signal to output an optical coherence imaging image.

4. The four-modality synchronous imaging system based on chirped pulse amplification according to claim 1, characterized in that: The broadened laser signal and the second amplified optical signal are merged into the first optical path transmission module, and then sequentially pass through the first optical path transmission module, the high-speed scanning module, and the second optical path transmission module to enter the image acquisition module, and excite the sample to be tested in the image acquisition module to generate an ultrasonic signal and an excitation optical signal respectively. The image acquisition module further separates the excitation optical signal to generate a first sample optical signal and a second sample optical signal, specifically including: The stretched laser signal and the second amplified optical signal are merged into the first optical path transmission module, and are expanded, collimated, and reflected by the first optical path transmission module, so that the stretched laser signal forms a first incident optical signal, and the second amplified optical signal forms a second incident optical signal; The high-speed scanning module performs scanning processing on the first incident light signal and the second incident light signal, so that the first incident light signal forms a first directional light signal, and the second incident light signal forms a second directional light signal; The second optical path conducting module conducts the first directional light signal and the second directional light signal, so that the first directional light signal and the second directional light signal enter the image acquisition module; The first directional light signal excites the sample to be tested in the image acquisition module to generate an ultrasonic signal, and the ultrasonic signal is converted into an ultrasonic electrical signal through the image acquisition module and sent to the photoacoustic signal processing module; the second directional light signal excites the sample to be tested to generate a sample excitation light signal, and the sample excitation light signal is separated through the image acquisition module to form a first sample light signal and a second sample light signal.

5. The four-modality synchronous imaging system based on chirped pulse amplification according to claim 4, characterized in that: The first light path transmission module includes: a first dichroic mirror, a plurality of lenses and a plurality of reflectors; the high-speed scanning module includes: one or more reflectors, a two-dimensional scanning device and a galvanometer; The broadened laser signal is reflected by the first dichroic mirror, and then sequentially undergoes beam expansion and collimation processing by the multiple lenses and multiple reflectors to form the first incident light signal; the second amplified light signal is transmitted by the first dichroic mirror, and then sequentially undergoes beam expansion and collimation processing by the multiple lenses and multiple reflectors to form the second incident light signal; wherein the first incident light signal and the second incident light signal are conducted in the same optical path; The one or more reflectors adjust the incident angles of the first incident light signal and the second incident light signal; the two-dimensional scanning device scans the first incident light signal and the second incident light signal in the X-axis direction, and the galvanometer scans the first incident light signal and the second incident light signal in the Y-axis direction, so that the first incident light signal forms a first directional light signal, and the second incident light signal forms a second directional light signal; the X-axis is perpendicular to the Y-axis; the second optical path transmission module includes a plurality of lenses and a plurality of reflectors, which are used to transmit the first directional light signal and the second directional light signal, so that the first directional light signal and the second directional light signal enter the image acquisition module; wherein, the first directional light signal and the second directional light signal are transmitted in the same optical path.

6. The four-modality synchronous imaging system based on chirped pulse amplification according to claim 4, characterized in that: The image acquisition module comprises: a second dichroic mirror, an objective lens, an ultrasonic transducer and a water tank; wherein the second dichroic mirror is placed above the objective lens; the ultrasonic transducer and the water tank are integrated on the objective lens; the ultrasonic transducer is annular and is placed on the lower surface of the objective lens or surrounds the side surface of the objective lens; the lower surface or the side surface of the objective lens and the ultrasonic transducer are immersed in the upper part of the water tank together; the sample to be tested is placed in the lower part of the water tank; After the first directional light signal and the second directional light signal pass through the second dichroic mirror and enter the objective lens, they act on the sample to be tested; The first directional light signal excites the sample to be tested to generate an ultrasonic signal, and converts the ultrasonic signal into an ultrasonic electrical signal through the ultrasonic transducer and sends it to the photoacoustic signal processing module; the second directional light signal excites the sample to be tested to generate a sample excitation light signal, and separates the sample excitation light signal through the second dichroic mirror to form a first sample light signal and a second sample light signal, so that the first sample light signal is reflected into the detection module, and the second sample light signal is transmitted into the second optical path conduction module.

7. The four-modality synchronous imaging system based on chirped pulse amplification according to claim 4, characterized in that: The detection module includes: a third dichroic mirror, a multi-photon detection device and a multiple harmonic detection device; wherein the multi-photon detection device includes a first photomultiplier tube; the multiple harmonic detection device includes a second photomultiplier tube; The third dichroic mirror separates the first sample light signal to form a fluorescence signal and a harmonic wave signal; The first photomultiplier tube detects and analyzes the fluorescence signal to generate a multiphoton imaging electrical signal, and sends the multiphoton imaging electrical signal to an external display device connected to the first photomultiplier tube; The second photomultiplier tube detects and analyzes the harmonic signal to generate a multiple harmonic imaging electrical signal, and sends the multiple harmonic imaging electrical signal to an external display device connected to the second photomultiplier tube.

8. The four-modality synchronous imaging system based on chirped pulse amplification according to claim 7, characterized in that: The multi-photon detection device further comprises a first band-pass filter; the multi-harmonic detection device comprises a second band-pass filter; The first bandpass filter is disposed between the third dichroic mirror and the first photomultiplier tube; the second bandpass filter is disposed between the third dichroic mirror and the second photomultiplier tube.

9. The four-modality synchronous imaging system based on chirped pulse amplification according to claim 1, characterized in that: The system also includes a main frame; a light source module, a photoacoustic light source widening module, an optical coherence imaging module, a first light path transmission module, a high-speed scanning module, a second light path transmission module, an image acquisition module, a detection module and a photoacoustic signal processing module are arranged in the main frame; The exterior of the main frame is provided with openings for conducting signal lines and power supply lines to the outside.

10. A method for using the chirped pulse amplification based quad-modal synchronous imaging system according to any one of claims 1 to 9, characterized in that: The four-modal synchronous imaging system based on chirped pulse amplification includes: a light source module, a photoacoustic light source broadening module, an optical coherence imaging module, a first light path transmission module, a high-speed scanning module, a second light path transmission module, an image acquisition module, a photoacoustic signal processing module and a detection module; the light source module includes: a chirped amplification laser and an optical parametric amplification laser; the method includes: The laser emitted by the chirped amplified laser is subjected to phase processing by the first half-wave plate and then to beam splitting processing by the first polarization beam splitter prism to generate a first laser signal and a second laser signal; The optical parametric amplifier laser acquires the first laser signal and forms a chirped amplified laser signal through chirped amplification processing; The photoacoustic light source widening module acquires the second laser signal and forms a widened laser signal after widening processing; The optical coherent imaging module acquires the chirped amplified laser signal, generates a first amplified optical signal and a second amplified optical signal through beam splitting processing, and further reflects the first amplified optical signal multiple times to form an interference reference optical signal; The first optical path transmission module sequentially performs beam expansion and collimation processing on the stretched laser signal and the second amplified optical signal, so that the stretched laser signal generates a first incident optical signal, and the second amplified optical signal generates a second incident optical signal; The high-speed scanning module acquires the first incident light signal and the second incident light signal, and after scanning processing, the first incident light signal forms a first directional light signal, and the second incident light signal forms a second directional light signal; The second optical path transmission module acquires the first directional light signal and the second directional light signal, and transmits the first directional light signal and the second directional light signal into the image acquisition module; The image acquisition module acquires the first directional light signal and the second directional light signal, the first directional light signal excites the sample to be tested in the image acquisition module to generate an ultrasonic signal, and the ultrasonic signal is converted into an ultrasonic electrical signal by the image acquisition module and sent to the photoacoustic signal processing module; the second directional light signal excites the sample to be tested to generate a sample excitation light signal, and the sample excitation light signal is separated by the image acquisition module to form a first sample light signal and a second sample light signal; The photoacoustic signal processing module collects the ultrasonic electrical signal, generates a photoacoustic microscopy imaging electrical signal after analysis and processing, and an external display device processes the photoacoustic microscopy imaging electrical signal to output a photoacoustic image; The detection module acquires the first sample light signal, forms a fluorescence signal and a harmonic signal through separation processing, detects the fluorescence signal to generate a multi-photon imaging electrical signal, and then sends the multi-photon imaging electrical signal to an external display device connected to the detection module, so that the external display device processes the multi-photon imaging electrical signal and outputs a fluorescence image, and detects the harmonic signal to generate multiple harmonic imaging electrical signals, so that the external display device processes the multiple harmonic imaging electrical signals and outputs a harmonic image; The optical coherence imaging module acquires the second sample light signal, and performs beam-combining interference processing on the second sample light signal and the interference reference light signal to generate an interference light signal, and then performs photoelectric conversion processing on the interference light signal to generate an optical coherence imaging electrical signal, which is used for an external display device to process the optical coherence imaging electrical signal and output an optical coherence imaging image.

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