Dual-scale photoacoustic microscopic imaging device integrating optical resolution and acoustic resolution

Abstract

The invention discloses a dual-scale photoacoustic microscopic imaging device integrating optical resolution and acoustic resolution to meet dual-scale imaging requirements of optical resolution and acoustic resolution, and the device comprises a laser emission module, a photoacoustic scanning and receiving module and a system control and signal processing module, by using the dual-scale photoacoustic microscopic imaging device integrating the optical resolution and the acoustic resolution, the advantages of high imaging resolution of an optical resolution photoacoustic microscopic system and deep imaging depth of an acoustic resolution photoacoustic microscopic system can be combined, and comprehensive imaging capability is provided at different resolutions and depths; the integration of biomedical research on structure and functional imaging is promoted, and the application potential of photoacoustic imaging in biomedicine and other fields is expanded.

Description

Technical Field

[0001] The invention belongs to the field of photoacoustic microscopy, and in particular relates to a dual-scale photoacoustic microscopy device integrating optical resolution and acoustic resolution. Background Art

[0002] Photoacoustic imaging is a new, non-destructive medical imaging technology that obtains two-dimensional tomographic or three-dimensional stereoscopic imaging of tissues based on the principle of photoacoustic effect. The advantage of this technology is that it can achieve high-resolution imaging and non-invasive observation of biological tissues. Therefore, this technology has been gradually applied to biomedical research and clinical diagnosis. As a typical photoacoustic imaging technology, photoacoustic microscopy can be divided into optical resolution photoacoustic microscopy (OR-PAM) and acoustic resolution photoacoustic microscopy (AR-PAM). In OR-PAM, since the incident light is strongly focused, the spot size can usually reach several microns, which is much smaller than the acoustic focus. The lateral resolution of the system depends on the optical focus, which can provide micron-level spatial resolution, but its imaging depth is limited by tissue light scattering, usually within a few hundred microns, and cannot effectively penetrate thicker tissues; on the contrary, in AR-PAM, since the light focused on the sample is weakly focused, the spot size is large, and the lateral resolution of the system depends on the acoustic focus with a smaller focus, which is smaller than OR-PAM. AP-PAM combines the photoacoustic effect and acoustic imaging technology, and takes advantage of the ability of ultrasound to penetrate tissues to achieve millimeter-level imaging depth to meet the needs of deep tissue imaging. Traditional photoacoustic microscopy devices can usually only image at a fixed scale (single resolution) and depth, which limits their ability to obtain rich information about biological tissues and makes it difficult to adapt to diverse imaging needs. Therefore, the development of a dual-scale photoacoustic microscopy device that integrates optical resolution and acoustic resolution is of significant importance to meet the needs of different imaging resolutions and imaging depths in in vivo imaging. This device will greatly expand the application range of photoacoustic imaging technology and provide more accurate imaging methods for medical diagnosis and biomedical research.

[0003] An innovative cross-scale photoacoustic imaging system (CN201811645701.5) is currently available. The system uses double-clad optical fiber and a switching device to achieve excitation light transmission in optical resolution and acoustic resolution imaging modes. Through the switching device, the photoacoustic signal is effectively received by the ultrasonic transducer, thereby performing high-quality imaging. However, the system has certain limitations, that is, it is impossible to simultaneously achieve photoacoustic microscopy imaging modes with optical resolution and acoustic resolution, resulting in certain limitations on imaging depth and resolution, affecting the application effect of the system in complex biological tissues.

[0004] An existing parallel multiscale photoacoustic microscopy method based on fiber delay (CN202010533612.2) uses optical fibers of different lengths and core diameters to generate laser pulses with different delays. In this way, photoacoustic data of different resolutions can be acquired during a single A-type scan, realizing parallel multiscale imaging from optical resolution to acoustic resolution. However, the disadvantage is that this method requires precise control of the delay intervals of multiple optical fibers and multiple laser pulses, which undoubtedly increases the complexity of the system and may lead to increased costs. Summary of the invention

[0005] The technical problem to be solved by the present invention is to provide a dual-scale photoacoustic microscopy imaging device that can integrate optical resolution and acoustic resolution in view of the above-mentioned deficiencies in the prior art. The device has a simple structure and low manufacturing cost. It can achieve efficient execution of dual-scale imaging of optical resolution and acoustic resolution while maintaining imaging depth and resolution, effectively meet the imaging requirements of different scales and depths, and provide a more advanced and economical imaging solution for medical diagnosis and biomedical research.

[0006] The present invention is achieved by at least one of the following technical solutions.

[0007] A dual-scale photoacoustic microscopy imaging device integrating optical resolution and acoustic resolution, including a laser emission module, a photoacoustic scanning and receiving module, and a system control and signal processing module;

[0008] The laser emission module generates light beams of different wavelengths required by the system. After being emitted from the optical fiber, the light beams enter the photoacoustic scanning and receiving module. The two light beams are transformed into coaxial light beams through a focusing lens group and a dichroic mirror or a reflector. The light beams are focused or diverged to irradiate the sample to be tested to generate photoacoustic signals. The signals are transmitted to the system control and signal processing module to realize data processing, storage and image reconstruction.

[0009] The system control and signal processing module also realizes the laser triggering in the laser emission module and the movement of the linear displacement stage in the photoacoustic scanning and receiving module.

[0010] Furthermore, the laser emission module includes a first pulse laser, a first fiber coupler, a second fiber coupler, a second pulse laser, a first optical fiber, and a second optical fiber; the laser emitted by the first pulse laser passes through the first fiber coupler and the first optical fiber in sequence to enter the photoacoustic scanning and receiving module, and the laser emitted by the second pulse laser passes through the second fiber coupler and the second optical fiber in sequence to enter the photoacoustic scanning and receiving module.

[0011] Furthermore, the first optical fiber is a multimode optical fiber, and the optical fiber is lengthened to generate a pulse delay; the second optical fiber is a single-mode optical fiber, and the interfaces are both FC / PC interfaces.

[0012] Furthermore, the photoacoustic scanning and receiving module includes a first double-glued lens, a second double-glued lens, a reflector, a dichroic mirror, a focusing lens, a prism group, an acoustic lens, a water tank, an ultrasonic transducer, and a linear translation stage; after the two light beams generated by the laser emission module pass through the first double-glued lens and the second double-glued lens respectively, one light beam is reflected by the reflector and then transmitted by the dichroic mirror, and the other light beam is reflected by the dichroic mirror. Both laser beams are irradiated on the sample to be tested through the focusing lens, the prism group, and the acoustic lens to generate photoacoustic signals, and the photoacoustic signals are received by the piezoelectric ultrasonic transducer through the water tank, the acoustic lens, and the prism group; the linear translation stage is fixed on the experimental table, and the movement of the linear translation stage is used to realize raster scanning to obtain photoacoustic data.

[0013] Furthermore, the photoacoustic signal is collected by an acoustic lens and transmitted to an ultrasonic transducer through a prism group;

[0014] The prism group is composed of two prisms whose inclined surfaces are bonded relative to each other. The acoustic lens is fixed on the prism group by ultraviolet curing glue to reduce the loss of acoustic energy. The ultrasonic transducer is bonded to the prism group by epoxy resin.

[0015] Furthermore, the ultrasonic transducer receives a photoacoustic signal generated by the photoacoustic effect when the laser is irradiated on the sample to be tested and focused by the acoustic lens.

[0016] Further, the sample to be tested is placed at the bottom of the water tank, a polyethylene film is placed above the sample to be tested, and a water layer of appropriate thickness is arranged above the polyethylene film.

[0017] Furthermore, the system control and signal processing module includes a host computer, a low-pass filter, and an amplifier; the photoacoustic signal generated by the photoacoustic scanning and receiving module is amplified by the amplifier, filtered by the low-pass filter, and stored in the host computer, and the host computer reconstructs the image after signal processing.

[0018] Furthermore, the linear translation stage includes three single-axis stepper motors and adopts open-loop control.

[0019] Furthermore, the host computer of the system control and signal processing module controls the first pulse laser and the second pulse laser of the laser emission module to emit laser pulses, collect data and control the moving speed and range of the linear translation stage.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] (1) The device of the present invention combines the advantages of optics and acoustics, effectively compensating for the shortcomings of single-scale imaging. This combination of multi-mode imaging can obtain more comprehensive biological tissue characteristics and provide more accurate and reliable information in biomedical research and clinical diagnosis.

[0022] (2) The device of the present invention integrates multiple imaging modes in the same system, so that the device can achieve deeper imaging of biological tissues while maintaining high resolution, greatly improving the comprehensive performance of photoacoustic microscopy imaging, and enabling photoacoustic microscopy imaging technology to demonstrate excellent imaging quality in different scenarios, thereby facilitating more accurate disease diagnosis and treatment monitoring.

[0023] (3) The device of the present invention has a simple structure, relatively low manufacturing cost, and is easy to implement and maintain. The low cost and easy operation make the device of the present invention have a wide range of practical application potentials and can meet different imaging needs. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 Schematic diagram of the structure of a dual-scale photoacoustic microscopy imaging device integrating optical resolution and acoustic resolution in an embodiment of the present invention;

[0025] Figure 2 This is a schematic diagram of a photoacoustic microprobe fixture of a photoacoustic scanning and receiving module of an embodiment;

[0026] Figure 3 A flow chart of a dual-scale photoacoustic microscopy imaging method integrating optical resolution and acoustic resolution is provided as an embodiment;

[0027] Among them, 1-laser emission module; 101-first pulse laser; 102-first fiber coupler; 103-second fiber coupler; 104-second pulse laser; 105-first optical fiber; 106-second optical fiber; 2-photoacoustic scanning and receiving module; 201-first double glued lens; 202-second double glued lens; 203-reflector; 204-dichroic mirror; 205-focusing lens; 206-prism group; 207-acoustic lens; 208-water tank; 209-ultrasonic transducer; 210-linear translation stage; 3-system control and signal processing module; 301-host computer; 302-low-pass filter; 303-amplifier; 4-fixed plate; 5-fiber adapter; 6-first lens fixture; 7-reflector fixing frame; 8-dichroic mirror fixing frame; 9-second lens fixture; 10-third lens fixture; 11-ultrasonic transducer fixing frame. DETAILED DESCRIPTION

[0028] In order to make the purpose, technical solutions and advantages of the present invention more clear, the present invention will be further described in detail below in conjunction with embodiments and drawings.

[0029] like Figure 1 to Figure 3As shown, a dual-scale photoacoustic microscopy imaging device integrating optical resolution and acoustic resolution includes a laser emitting module 1, a photoacoustic scanning and receiving module 2, and a system control and signal processing module 3; wherein the laser emitting module 1 generates light beams of different wavelengths required by the system, and the light beams enter the photoacoustic scanning and receiving module 2 after being emitted from the optical fiber; the two light beams are transformed into coaxial light beams through a focusing lens group and a dichroic mirror or a reflector, and the light beams are focused or diverged to irradiate a sample to be tested to generate a photoacoustic signal, and the signal is transmitted to the system control and signal processing module 3 to realize data processing, storage and image reconstruction; the system control and signal processing module 3 can also realize laser triggering in the laser emitting module 1 and control the movement of the linear displacement stage on the photoacoustic scanning and receiving module 2.

[0030] In this embodiment, the first fiber coupler and the second fiber coupler couple the laser from the pulse laser into the optical fiber for transmission. The host computer 301 controls the repetition frequency, output power and wavelength of the first pulse laser 101 and the second pulse laser 104. The first pulse laser 101 emits a laser with a wavelength of 1064nm, which is coupled to the first optical fiber 105 through the first fiber coupler 102. At the same time, a pulse delay is generated by lengthening the optical fiber. After the light beam is emitted from the optical fiber, it enters the photoacoustic scanning and receiving module 2. The light beam diverges and irradiates the sample to be tested to achieve AR-PAM imaging; the second pulse laser 104 emits a laser with a wavelength of 532nm, which is coupled to the second optical fiber 106 of 2m through the second optical fiber coupler 103. After the light beam is emitted from the optical fiber, it enters the photoacoustic scanning and receiving module 2. The light beam is focused and irradiated on the sample to be tested to achieve OR-PAM imaging; one end of the first optical fiber 105 and the second optical fiber 106 are respectively connected to the first optical fiber coupler 102 and the second optical fiber coupler 103, and the other end is fixed at different heights to achieve the output of two light beams. Since the first optical fiber 105 and the second optical fiber 106 have different lengths, light beams with different pulse delays can be output.

[0031] The first pulse laser 101 and the second pulse laser 104 have a repetition frequency of up to 1.5 MHz and an average power of up to 30 W. The first pulse laser 101 outputs a laser with a wavelength of 1064 nm for AR-PAM imaging, and the second pulse laser 104 outputs a laser with a wavelength of 532 nm for OR-PAM imaging.

[0032] As an embodiment, the first optical fiber 105 is a multi-mode optical fiber, and the optical fiber is lengthened to generate a pulse delay. The second optical fiber 106 is a single-mode optical fiber, and the interfaces are both FC / PC interfaces.

[0033] The photoacoustic scanning and receiving module 2 is a dual-scale photoacoustic scanning and receiving module with optical resolution and acoustic resolution, including a first double-cemented lens 201, a second double-cemented lens 202, a reflector 203, a dichroic mirror 204, a focusing lens 205, a prism group 206, an acoustic lens 207, a water tank 208, an ultrasonic transducer 209, and a linear translation stage 210; after the two light beams pass through the double-cemented lenses respectively, one light beam is reflected by the reflector 203 and then transmitted by the dichroic mirror 204, and the other light beam is reflected by the dichroic mirror 204, and the two laser beams are irradiated on the sample to be tested through the focusing lens 205, the prism group 206, and the acoustic lens 207, so that it generates a photoacoustic signal, and the signal passes through the water tank 208, the acoustic lens 207, and the prism group 206 and is received by the ultrasonic transducer 209.

[0034] In this embodiment, the reflector 203 is silver-coated with an average reflectivity greater than 97%, and is fixed to the base by epoxy resin. The photoacoustic signal is collected by the acoustic lens 207 and transmitted to the ultrasonic transducer 209 through the prism group 206; the prism group 206 is composed of two prisms with inclined surfaces facing each other and bonded together by UV curing glue, wherein the prism located at the bottom is aluminum-coated, the acoustic lens 207 is fixed to the prism group 206 by UV curing glue to reduce the loss of acoustic energy, and the ultrasonic transducer 209 is bonded to the prism group 206 by epoxy resin. The linear displacement stage 210 is fixed on the experimental table, and the movement of the linear displacement stage is used to realize raster scanning to obtain photoacoustic data.

[0035] like Figure 2 The schematic diagram of the photoacoustic scanning and receiving module photoacoustic microprobe fixture is shown. The fixed plate 4 serves as a supporting component and provides a mounting platform for other components. The first lens fixture 6, the second lens fixture 9 and the third lens fixture 10 are respectively mounted on the fixed plate 4 to clamp and fix the first double-cemented lens 201, the focusing lens 205 and the second double-cemented lens 202; the first lens fixture 6 and the third lens fixture 10 are fixedly connected with the optical fiber adapter 5 to ensure that the optical fiber is accurately connected with the optical path of the first double-cemented lens 201 and the second double-cemented lens 202 to achieve stable transmission of the laser. The fixed plate 4 is also equipped with a reflector fixing frame 7, a dichroic mirror fixing frame 8 and an ultrasonic transducer fixing frame 11. The reflector fixing frame 7 is used to fix the reflector 203 so that the 1064nm laser propagates along the predetermined path. The dichroic mirror fixing frame 8 is used to fix the dichroic mirror 204 to ensure that the 1064nm and 532nm lasers propagate along the predetermined path. The ultrasonic transducer fixing frame 11 is used for installing the ultrasonic transducer.

[0036] As an embodiment, the center frequency of the ultrasonic transducer 209 is 50 MHz, the bandwidth is 40 MHz, and what is received is the photoacoustic signal generated by the laser irradiating the sample to be tested and focused by the acoustic lens 207 .

[0037] To ensure that the photoacoustic signal can be effectively received, the sample to be tested is placed at the bottom of the water tank 208, the polyethylene film is placed above the sample to be tested, and a water layer of appropriate thickness is set above the polyethylene film. Water has excellent sound wave propagation characteristics and can effectively transmit the photoacoustic signal to the ultrasonic transducer 209, so water is used as the photoacoustic coupling medium for non-contact measurement.

[0038] The system control and signal processing module 3 includes a host computer 301, a low-pass filter 302, and an amplifier 303; the received photoacoustic signal is amplified by the amplifier 303, filtered by the low-pass filter 302 and stored in the host computer 301, and the host computer 301 reconstructs the image after signal processing; at the same time, the host computer 301 also controls the first laser 101 and the second pulse laser 104 to emit laser pulses, collect data and control the moving speed and range of the linear translation stage 210.

[0039] The linear translation stage 210 is fixed on the experimental table, and the movement of the linear translation stage is used to realize raster scanning to obtain photoacoustic data. The linear translation stage 210 includes three single-axis stepper motors, which are used for photoacoustic scanning and precise linear movement of the receiving module 2 in three dimensions, respectively, and adopts open-loop control.

[0040] The linear translation stage 210 is directly connected to the probe fixture of the photoacoustic scanning and receiving module 2, and the precise linear movement of the photoacoustic microprobe in the three dimensions of X, Y, and Z is realized through the coordinated operation of three uniaxial stepper motors. This precise mobile scanning relationship enables the system to obtain photoacoustic signals at different depths and positions, ensuring the comprehensiveness and accuracy of imaging. The system control and signal processing module 3 controls the motion path of the three uniaxial stepper motors through the host computer 301, and triggers the first pulse laser 101 and the second pulse laser 104 in the laser emission module 1 to emit pulsed lasers each time the stepper motor moves to a new position. At the same time, the ultrasonic transducer 209 is triggered to receive the photoacoustic signal and control the moving speed and range of the linear translation stage. The pulsed laser is transmitted to the photoacoustic scanning and receiving module 2 through the optical path, and the sample to be tested absorbs the laser and generates a photoacoustic signal, and then the ultrasonic transducer 209 is responsible for receiving these signals. In order to ensure the accuracy of signal acquisition, the system control and signal processing module 3 uses a synchronous signal mechanism to ensure that the photoacoustic scanning and receiving module 2 performs data acquisition at the appropriate time so as to correspond to the emission position of the pulsed laser, thereby achieving accurate matching of the timing and spatial relationship of the signal.

[0041] The host computer 301 controls the scanning speed and range of the linear translation stage 208. The ultrasonic transducer 209 receives the photoacoustic signal after focusing with the acoustic lens 207. The photoacoustic signal is received by the ultrasonic transducer 209 and converted into an electrical signal. The signal is stored in the host computer 301 after passing through the amplifier 303 and the low-pass filter 302. The amplifier 303 amplifies the signal by 48 dB. The cutoff frequency of the low-pass filter 302 is 70 MHz. The host computer 301 collects the signal at a frequency of 200 MHz with a sampling accuracy of 14 bits. After the scanning of the entire imaging area is completed, signal processing and image reconstruction are performed in the host computer 301. The trigger signal for data acquisition is sent by the host computer 301.

[0042] Although the embodiments disclosed in the present invention are as above, the above contents are only embodiments adopted for facilitating the understanding of the present invention and are not intended to limit the present invention. Any technician in the technical field to which the present invention belongs can make any modifications and changes in the form and details of the implementation without departing from the spirit and scope disclosed in the present invention, but the patent protection scope of the present invention shall still be subject to the scope defined in the attached claims.

Claims

1. A dual-scale photoacoustic microscopy imaging device integrating optical resolution and acoustic resolution, characterized in that: It comprises a laser emission module (1), a photoacoustic scanning and receiving module (2), and a system control and signal processing module (3); The laser emission module (1) generates light beams of different wavelengths required by the system. After being emitted from the optical fiber, the light beams enter the photoacoustic scanning and receiving module (2). The two light beams are transformed into coaxial light beams through a focusing lens group and a dichroic mirror or a reflector. The light beams are focused or diverged to irradiate the sample to be tested to generate photoacoustic signals. The signals are transmitted to the system control and signal processing module (3) to realize data processing, storage and image reconstruction. The system control and signal processing module (3) also realizes the laser triggering in the laser emission module (1) and the photoacoustic scanning and movement of the linear displacement stage in the receiving module (2).

2. The dual-scale photoacoustic microscopy imaging device integrating optical resolution and acoustic resolution according to claim 1, characterized in that: The laser emission module (1) comprises a first pulse laser (101), a first optical fiber coupler (102), a second optical fiber coupler (103), a second pulse laser (104), a first optical fiber (105), and a second optical fiber (106); the laser emitted by the first pulse laser (101) sequentially passes through the first optical fiber coupler (102) and the first optical fiber (105) to enter the photoacoustic scanning and receiving module (2), and the laser emitted by the second pulse laser (104) sequentially passes through the second optical fiber coupler (103) and the second optical fiber (106) to enter the photoacoustic scanning and receiving module (2).

3. The dual-scale photoacoustic microscopy imaging device integrating optical resolution and acoustic resolution according to claim 2, characterized in that: The first optical fiber (105) is a multi-mode optical fiber, and the optical fiber is lengthened to generate pulse delay; the second optical fiber (106) is a single-mode optical fiber, and the interfaces are all FC / PC interfaces.

4. The dual-scale photoacoustic microscopy imaging device integrating optical resolution and acoustic resolution according to claim 1, characterized in that: The photoacoustic scanning and receiving module (2) comprises a first double-cemented lens (201), a second double-cemented lens (202), a reflector (203), a dichroic mirror (204), a focusing lens (205), a prism group (206), an acoustic lens (207), a water tank (208), an ultrasonic transducer (209), and a linear translation stage (210); after two light beams generated by the laser emission module (1) pass through the first double-cemented lens (201) and the second double-cemented lens (202) respectively, one light beam is reflected by the reflector (203) and then The dichroic mirror (204) transmits the other beam of light, and the dichroic mirror (204) reflects the other beam of light. The two laser beams are irradiated on the sample to be tested through a focusing lens (205), a prism group (206), and an acoustic lens (207), so that the sample generates a photoacoustic signal. The photoacoustic signal is received by a piezoelectric ultrasonic transducer (209) through a water tank (208), an acoustic lens (207), and a prism group (206). The linear displacement stage (210) is fixed on the experimental table, and raster scanning is realized by the movement of the linear displacement stage (210) to obtain photoacoustic data.

5. The dual-scale photoacoustic microscopy imaging device integrating optical resolution and acoustic resolution according to claim 4, characterized in that: The photoacoustic signal is collected by an acoustic lens (207) and transmitted to an ultrasonic transducer (209) through a prism group (206); The prism group (206) is formed by bonding the inclined surfaces of two prisms relative to each other, the acoustic lens (207) is fixed on the prism group (206) by using ultraviolet curing glue to reduce acoustic energy loss, and the ultrasonic transducer (209) is bonded to the prism group (206) by epoxy resin.

6. The dual-scale photoacoustic microscopy imaging device integrating optical resolution and acoustic resolution according to claim 4, characterized in that: The ultrasonic transducer (209) receives a photoacoustic signal generated by the photoacoustic effect when the laser is irradiated on the sample to be tested and focused by the acoustic lens (207).

7. The dual-scale photoacoustic microscopy imaging device integrating optical resolution and acoustic resolution according to claim 6, characterized in that: The sample to be tested is placed at the bottom of the water tank (208), a polyethylene film is placed above the sample to be tested, and a water layer of appropriate thickness is arranged above the polyethylene film.

8. The dual-scale photoacoustic microscopy imaging device integrating optical resolution and acoustic resolution according to claim 1, characterized in that: The system control and signal processing module (3) comprises a host computer (301), a low-pass filter (302), and an amplifier (303); the photoacoustic signal generated by the photoacoustic scanning and receiving module (2) is amplified by the amplifier (303), filtered by the low-pass filter (302), and then stored in the host computer (301); the host computer (301) reconstructs the image after signal processing.

9. The dual-scale photoacoustic microscopy imaging device integrating optical resolution and acoustic resolution according to claim 4, characterized in that: The linear translation stage comprises three single-axis stepper motors and adopts open-loop control.

10. The dual-scale photoacoustic microscopy imaging device integrating optical resolution and acoustic resolution according to any one of claims 4 to 9, characterized in that: The host computer (301) of the system control and signal processing module (3) controls the first pulse laser (101) and the second pulse laser (104) of the laser emission module (1) to emit laser pulses, collect data, and control the moving speed and range of the linear displacement stage (210).

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