A cross-scale photoacoustic imaging system

Abstract

The present application relates to the technical field of biomedical image imaging, and discloses a cross-scale photoacoustic imaging system, which comprises a laser emission module, a zoom module, a laser excitation module and a signal acquisition module. The zoom module achieves at least two focusing modes on the sample by changing the focal length, and the two focusing modes include a strong focusing mode (corresponding to OR-PAM) and a weak focusing mode (corresponding to AR-PAM). The pulsed laser emitted by the laser emission module is sequentially irradiated onto the sample through the zoom module and the laser excitation module and excites photoacoustic signals, and the photoacoustic signals are received by the signal acquisition module. When the system works as OR-PAM, imaging can be performed at the cell scale; when the system works as AR-PAM, imaging can be performed on structures such as blood vessels and joints at the macroscopic level, thereby realizing the cross-scale imaging function in the field of photoacoustic imaging. Moreover, the cross-scale photoacoustic imaging system is free of optical fibers, light splitting and light cutting, the whole system is simple in structure, easy to build, not complicated and low in cost.

Description

Technical Field

[0001] This invention relates to the technical field of biomedical imaging, and more specifically, to a multi-scale photoacoustic imaging system. Background Technology

[0002] In modern biology, as research focus has shifted from probing the morphological phenotypes of living organisms to quantitatively measuring fundamental cellular and molecular mechanisms, this shift has directly led to a continuous increase in the demand for information throughput in bio-optical imaging. For example, neurons, as the fundamental building blocks of the brain and nervous system, are typically on the order of micrometers in size, but their functional connections extend throughout the entire brain. To study the working mechanisms of the entire nervous system, it is necessary to simultaneously perform high-resolution imaging of every neuron within the entire brain.

[0003] For example, research applications in cell biology, rapid clinical diagnosis, drug screening, and cell function analysis require both rapid and non-invasive functional testing of populations of living cells and dynamic functional analysis of single cells at the subcellular and molecular levels to interpret fundamental cellular functions. To achieve imaging of such life science systems at different scales, cross-scale imaging techniques are essential.

[0004] In recent years, rheumatoid arthritis (RA) has become increasingly prevalent among middle-aged and elderly people. Research on early RA lesions requires in vivo observation of cross-scale physiological information such as immune cell dynamics, blood vessels, inflammation distribution, and joint structure. However, there are very few cross-scale imaging technologies available at present.

[0005] Traditional photoacoustic microscopy (PAM) systems are mainly classified into optical resolution photoacoustic microscopy (OR-PAM) systems and acoustic resolution photoacoustic microscopy (AR-PAM) systems based on imaging resolution. OR-PAM is characterized by an excitation spot diameter smaller than the focal spot of the ultrasound transducer, thus its imaging resolution depends on the size of the excitation spot. OR-PAM offers high resolution, ranging from hundreds of nanometers to several micrometers, but has a shallow imaging depth of approximately 1-2 mm, allowing for observation of cell dynamics. AR-PAM, on the other hand, has a much larger excitation spot than the ultrasound transducer's detection area, so its imaging resolution depends on the size of the ultrasound transducer's focal spot. AR-PAM has a large imaging depth of several centimeters, but its resolution is lower than OR-PAM, reaching only a few hundred micrometers. However, it can be used to observe the morphology and distribution of blood vessels, as well as joint structures.

[0006] However, current imaging technologies mostly focus on specialized functional extensions for a single purpose, failing to obtain useful information at both scales. Therefore, multi-scale imaging is an urgent need for basic research and clinical diagnosis, and represents a new trend in the development of current imaging technologies.

[0007] Photoacoustic imaging is a major revolutionary technology in the field of biomedical imaging. Its unique advantages of optical excitation and acoustic detection hold promise as a natural link between macroscopic clinical ultrasound imaging and microscopic basic research fluorescence imaging. Photoacoustic imaging technology acquires tissue light absorption information by detecting the ultrasound signal generated by the transient thermoelastic effect after biological tissue absorbs pulsed laser light. It can perform label-free, quantitative functional imaging of physiological parameters such as blood flow and blood oxygenation based on endogenous hemoglobin; it can also reveal information such as the metabolic state and inflammation distribution of RA tissue using exogenous molecular probes.

[0008] In 2013, Wang Lihong's research group at the University of Washington pioneered the concept of multi-scale photoacoustic microscopy, achieving this technology using fiber bundles. However, the high cost and maintenance difficulties of the fiber bundles resulted in a substantial system cost and expensive repairs. Furthermore, the system only allows for the use of a single ultrasonic transducer, meaning it can only acquire photoacoustic signals in a single frequency band, thus limiting its application scope.

[0009] In 2014, the Estrada research group in Germany also proposed a multi-scale photoacoustic microscopy imaging system. However, unlike the system of Wang Lihong's research group, their system utilizes the distance between a movable single-mode fiber and a self-focusing lens to achieve multi-scale microscopy imaging. But the ultrasonic transducer of this system requires an opening, which leads to a significant reduction in the detection efficiency of the ultrasonic transducer.

[0010] In 2014, Professor Luo Qingming's research group at Huazhong University of Science and Technology also proposed a multi-scale photoacoustic microscopy imaging system. Utilizing an electrically controlled zoom lens and imaging fiber bundle, they achieved a multi-scale photoacoustic microscopy imaging system with continuously adjustable resolution. However, this system uses a transmission-type signal acquisition method, which limits the range and size of the imaged object; it cannot image large objects with thicknesses on the centimeter scale. Furthermore, the system uses an expensive fiber bundle, resulting in high overall system cost and maintenance expenses.

[0011] In 2018, Professor Junjie Yao's research group at Duke University proposed a four-modal multiscale photoacoustic microscopy system. The most significant feature of this system is that both the light and acoustic spots can be altered. However, the ultrasonic transducers used in this system all have a centrally located opening, which significantly reduces their receiving efficiency. Furthermore, only two ultrasonic transducers can be connected to the system, thus limiting it to only two frequencies.

[0012] In 2020, Song Liang's research group at the Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, proposed a cross-scale photoacoustic microscopy imaging system based on double-clad optical fibers and coupling lenses. This system achieves cross-scale photoacoustic imaging by adjusting the coupling lens to couple a laser spot to different locations in the core and inner cladding of the double-clad fiber. However, the coupling of the double-clad fiber in this system is extremely difficult, requiring the laser to be simultaneously and completely coupled to both the core and the inner cladding, making its operation highly challenging. Furthermore, it cannot achieve continuously adjustable resolution.

[0013] In summary, the shortcomings of existing technologies are concentrated in the following aspects: 1. The use of fiber bundles results in high system costs and maintenance prices; 2. The need to adjust fiber coupling makes operation cumbersome and difficult; 3. The core concept is to combine two optical paths into one, resulting in redundancy and complexity of the entire system and making it difficult to build; 4. The resolution of most systems cannot be adjusted, resulting in fixed-resolution imaging. Summary of the Invention

[0014] The purpose of this invention is to provide a multi-scale photoacoustic imaging system, which aims to solve the problem of high system cost caused by the use of fiber bundles in existing multi-scale photoacoustic imaging systems.

[0015] This invention is implemented as follows: a multi-scale photoacoustic imaging system includes a laser emission module, a zoom module, a laser excitation module, and a signal acquisition module. The laser emission module emits pulsed laser light. The zoom module achieves at least two focusing modes on the sample by changing the focal length. The two focusing modes include a strong focusing mode and a weak focusing mode. The pulsed laser light emitted by the laser emission module passes sequentially through the zoom module and the laser excitation module before irradiating the sample and exciting a photoacoustic signal, which is received by the signal acquisition module. In the strong focusing mode, the multi-scale photoacoustic imaging system is an optical resolution photoacoustic microscopy system; in the weak focusing mode, the multi-scale photoacoustic imaging system is an acoustic resolution photoacoustic microscopy system.

[0016] Optionally, the laser emitting module includes a laser and a first collimation module. The pulsed laser emitted by the laser is collimated and expanded by the first collimation module before being incident on the zoom module.

[0017] Optionally, the laser excitation module includes a high-speed scanning galvanometer, on which the laser emitted from the zoom module irradiates the high-speed scanning galvanometer and then enters the objective lens to be focused on the sample.

[0018] Optionally, the signal acquisition module includes an ultrasonic transducer and a data information acquisition unit, wherein the ultrasonic transducer receives the photoacoustic signal and transmits the photoacoustic signal to the data information acquisition unit.

[0019] Optionally, the zoom module includes a liquid lens. The focal length of the liquid lens changes when the applied external voltage is changed, and the refractive power range of the liquid lens is -5 to +15.

[0020] Optionally, the zoom module further includes a first lens, onto which the laser emitted from the liquid lens is incident; the omnidirectional scanning range of the multi-scale photoacoustic imaging system Where M is the magnification from the sample plane to the image plane behind the liquid lens, n is the refractive index of the immersion medium in the liquid lens, f1 is the focal length of the first lens, and fli is the focal length of the liquid lens.

[0021] Optionally, the zoom module further includes a second collimation module, through which the laser emitted from the first lens is collimated and then incident on the laser excitation module.

[0022] Optionally, the liquid lens can be modified by applying mechanical pressure instead of external voltage to change its shape, thereby changing the focal length of the liquid lens.

[0023] Optionally, the liquid lens includes a lens cavity, the light-emitting side of the lens cavity has an elastic film, the lens cavity contains an optical liquid, and the pressure inside the lens cavity is controlled by the entry and exit of the optical liquid, thereby changing the focal length of the liquid lens.

[0024] Optionally, the liquid lens is an adjustable acoustic gradient lens.

[0025] Compared with existing technologies, this invention provides a cross-scale photoacoustic imaging system that uses a zoom module to change the focal length, thereby achieving strong focusing and weak focusing modes on the sample. This allows for switching between optical resolution photoacoustic microscopy (OR-PAM) and acoustic resolution photoacoustic microscopy (AR-PAM) imaging based on a single optical path. When operating as an OR-PAM, this cross-scale photoacoustic imaging system can perform imaging at the cellular level; when operating as an AR-PAM, it can image structures such as blood vessels and joints at the macroscopic level, thus realizing cross-scale imaging capabilities in the field of photoacoustic imaging. Furthermore, this cross-scale photoacoustic imaging system is fiber-free, beam-splitting, and beam-cutting-free, with a simple and easy-to-build structure that is not complex and has low cost. Attached Figure Description

[0026] Figure 1 This is a three-dimensional schematic diagram of a cross-scale photoacoustic imaging system provided by the present invention;

[0027] Figure 2 This is a schematic diagram of the optical path of a cross-scale photoacoustic imaging system provided by the present invention;

[0028] Figure 3 This is a schematic diagram of the optical path of the laser emission module of a cross-scale photoacoustic imaging system provided by the present invention;

[0029] Figure 4a This is a schematic diagram of the optical path of the zoom module of a cross-scale photoacoustic imaging system provided by the present invention;

[0030] Figure 4b This is a schematic diagram illustrating the change in photoacoustic imaging of a cross-scale photoacoustic imaging system as the curvature of the liquid lens changes, as provided by the present invention.

[0031] Figure 5 This is a schematic diagram of the optical path of the laser excitation module of a cross-scale photoacoustic imaging system provided by the present invention;

[0032] Figure 6 This is a schematic diagram of the optical path of the information acquisition module of a cross-scale photoacoustic imaging system provided by the present invention.

[0033] Explanation of reference numerals in the attached figures:

[0034] 101-Laser emitting module, 102-Zoom module, 103-Laser excitation module, 104-Signal acquisition module; 201-Laser, 202-Front convex lens, 203-Rear convex lens; 301-Liquid lens, 302-Cemented doublet lens, 303-Third convex lens, 304-Fourth convex lens; 401-High-speed scanning galvanometer, 402-Objective lens; 501-Ultrasonic transducer, 502-Data acquisition device. Detailed Implementation

[0035] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0036] The implementation of the present invention will be described in detail below with reference to specific embodiments.

[0037] In the accompanying drawings of this embodiment, the same or similar reference numerals correspond to the same or similar components. In the description of this invention, it should be understood that if terms such as "upper," "lower," "left," and "right" indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, they are only for the convenience of describing this invention and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, the terms used to describe positional relationships in the drawings are only for illustrative purposes and should not be construed as limiting this invention. For those skilled in the art, the specific meaning of the above terms can be understood according to the specific circumstances.

[0038] Reference Figure 1-6The image shown is a preferred embodiment of the present invention.

[0039] A multi-scale photoacoustic imaging system includes a laser emission module 101, a zoom module 102, a laser excitation module 103, and a signal acquisition module 104; the laser emission module 101 is used to emit pulsed lasers;

[0040] The zoom module 102 achieves at least two focusing modes on the sample by changing the focal length. The two focusing modes include a strong focusing mode and a weak focusing mode.

[0041] The pulsed laser emitted by the laser emitting module 101 passes through the zoom module 102 and the laser excitation module 103 in sequence before irradiating the sample and exciting a photoacoustic signal, which is received by the signal acquisition module 104.

[0042] In the strong focusing mode, the cross-scale photoacoustic imaging system is an optical resolution photoacoustic microscopy system (OR-PAM); in the weak focusing mode, the cross-scale photoacoustic imaging system is an acoustic resolution photoacoustic microscopy system (AR-PAM).

[0043] The key feature of OR-PAM is that the diameter of the excitation spot in the system is smaller than the focal spot of the ultrasound transducer, so the imaging resolution of this system depends on the size of the excitation spot. OR-PAM has high resolution, ranging from hundreds of nanometers to several micrometers, but a shallow imaging depth of about 1-2 mm, making it suitable for observing cell dynamics. AR-PAM, on the other hand, has a much larger spot size than the ultrasound transducer's detection area, so its imaging resolution depends on the size of the ultrasound transducer's focal spot. AR-PAM has a large imaging depth of about several centimeters, but its resolution is lower than OR-PAM, reaching only a few hundred micrometers. However, it can be used to observe the morphology and distribution of blood vessels, as well as joint structures, etc.

[0044] This embodiment provides a cross-scale photoacoustic imaging system that uses a zoom module 102 to change the focal length, thereby achieving strong focusing and weak focusing modes on the sample. This allows for switching between optical resolution photoacoustic microscopy (OR-PAM) and acoustic resolution photoacoustic microscopy (AR-PAM) imaging based on a single optical path. When operating as an OR-PAM, this cross-scale photoacoustic imaging system can perform imaging at the cellular level; when operating as an AR-PAM, it can image structures such as blood vessels and joints at the macroscopic level, thus realizing cross-scale imaging capabilities in the field of photoacoustic imaging. Furthermore, this cross-scale photoacoustic imaging system is fiber-free, beam-splitting, and beam-cutting-free, with a simple and easy-to-build structure that is not complex and has low cost.

[0045] Specifically, the laser emitting module 101 includes a laser 201 and a first collimation module. The pulsed laser emitted by the laser 201 is collimated and expanded by the first collimation module before being incident on the zoom module 102.

[0046] For example, the first collimation module can typically consist of two convex lenses, namely a front convex lens 202 and a rear convex lens 203. The two convex lenses have different focal lengths; along the laser transmission direction, the focal length of the front convex lens 202 is smaller than that of the rear convex lens 203; and the rear focal point of the front convex lens 202 coincides with the front focal point of the rear convex lens 203. After the laser beam passes through the first collimation module, it is collimated and expanded, so that the diameter of the beam emitted from the first collimation module matches the size of the zoom module 102 used subsequently. The pulsed laser emitted by the laser emitting module 101 will be incident horizontally and without convergence onto the zoom module 102.

[0047] The laser excitation module 103 includes a high-speed scanning galvanometer 401. The laser emitted from the zoom module 102 irradiates the high-speed scanning galvanometer 401. The high-speed scanning galvanometer 401 can quickly change the position of the focal point in two directions, thereby achieving the effect of point scanning. Subsequently, the laser is incident on the objective lens 402, and the objective lens 402 focuses the laser onto the sample plane.

[0048] In existing technology, the principle of optical scanning galvanometers is as follows: When a position signal is input, the oscillating motor (laser galvanometer) oscillates by a certain angle according to a specific voltage-to-angle conversion ratio. The entire process employs closed-loop feedback control, with five major control circuits working together: a position sensor (transducer), an error amplifier, a power amplifier (the amount of work done by an object per unit time), a position distinguisher, and an electronflow integrator. The principle of digital laser galvanometers, on the other hand, is to convert analog signals into digital signals, building upon the principle of analog laser galvanometers.

[0049] The high-speed scanning galvanometer 401 works by incidenting a laser beam onto two reflecting mirrors (scanning mirrors). The reflection angles of the mirrors are controlled by a computer, allowing them to scan along the X and Y axes respectively. This deflection of the laser beam allows the laser focal point, with a certain power density, to move as required on the sample plane. In this embodiment, the laser emitted from the zoom module 102 irradiates the high-speed scanning galvanometer 401. The high-speed scanning galvanometer 401 can rapidly change the position of the focal point in two directions, thus achieving a point scanning effect.

[0050] The laser excitation module also includes a relay lens group, which can be composed of two convex lenses with the same focal length and confocal. The back apertures of the high-speed scanning galvanometer, the relay lens group, and the objective lens (corresponding to the aperture at which the laser is incident on the objective lens) form a 4f conjugate relationship.

[0051] In one embodiment, the zoom module 102 includes a liquid lens 301. After changing the applied external voltage, the focal length of the liquid lens 301 changes, and the refractive power range of the liquid lens 301 is -5 to +15.

[0052] By changing the focal length of the liquid lens 301 through an applied voltage, the zoom of the entire multi-scale photoacoustic imaging system can be achieved. When the multi-scale photoacoustic imaging system needs to observe samples under conditions of different depths and scales, changing the applied voltage of the liquid lens 301 alters the focal plane and focal spot size of the multi-scale photoacoustic imaging system, thereby achieving multi-scale photoacoustic imaging.

[0053] The refractive power range of the liquid lens 301 is -5 to +15. Within the adjustment range of the liquid lens 301, the laser under the objective lens 402 can achieve two focusing modes: strong focusing on the sample and weak focusing on the sample.

[0054] The zoom module 102 also includes a first lens, for example, a cemented doublet lens 302, through which laser light emitted from the liquid lens 301 is incident; the multi-scale photoacoustic imaging system has an omnidirectional scanning range.

[0055] Where M is the magnification from the sample plane to the image plane behind the liquid lens 301, n is the refractive index of the immersion medium in the liquid lens 301, f1 is the focal length of the first lens, and f 液 It is the focal length of the liquid lens 301.

[0056] The calculations using the above formulas can quantify the axial scanning range of a multi-scale photoacoustic imaging system, providing data reference for sample preparation. Furthermore, combining these formulas with those from the photoacoustic field allows for the calculation of the theoretical optical or acoustic resolution of the liquid lens system at different focal lengths, thus making the system parameters more complete for user reference.

[0057] Specifically, the liquid lens 301 can change its focal length by adjusting its own radius of curvature. The change in curvature can be controlled by different physical mechanisms, such as electrowetting effect and liquid filling. The principle of electrowetting effect is to change the contact angle between the droplet and the solid medium by applying voltage to the contact surface between the droplet and the solid. When the applied voltage changes, the contact angle between the solid and the liquid changes, and the curvature of the liquid lens 301 also changes accordingly.

[0058] The focal length of the liquid lens 301 can be changed not only by applying an external voltage, but also by other means. For example, in another embodiment, mechanical pressure can be used instead of applying an external voltage to change the shape of the liquid lens 301, thereby changing the focal length of the liquid lens 301.

[0059] For example, the liquid lens 301 includes a lens cavity with an elastic film on the light-emitting side. The lens cavity contains an optical liquid, and the pressure within the lens cavity is controlled by the inflow and outflow of the optical liquid, thus changing the focal length of the liquid lens 301. When the optical liquid is injected into the lens cavity, a positive pressure is generated, causing the elastic film to bulge outwards under the pressure difference, forming a convex lens. Conversely, when the optical liquid is extracted from the lens cavity, a negative pressure is generated, forming a concave lens. By controlling the pressure within the cavity through the inflow and outflow of the liquid, the focal length of the liquid lens 301 can be adjusted.

[0060] The liquid lens 301 can also be an adjustable acoustic gradient lens. Its principle is to use sound waves generated by piezoelectric materials to radially excite a cylindrical cavity filled with a refractive fluid and have two flat glass windows, achieving ultra-high-speed changes in focal length. The cylindrical piezoelectric element generates sound waves with a specific driving frequency (t=0) on the flat glass wall through a strong radial vibration mode. These waves propagate back and forth between the two flat glass windows, interfering with each other to reach a stable state and generating standing wave oscillations of a certain density in the refractive fluid. Therefore, by controlling the driving frequency, a specific standing wave density oscillation can be obtained, thereby achieving a continuously variable refractive index and focal length, with a zoom time as low as microseconds or even shorter.

[0061] The zoom module 102 also includes a second collimation module. The laser emitted from the first lens is collimated by the second collimation module before being incident on the laser excitation module 103. Similar to the first collimation module, the second collimation module also consists of two confocal convex lenses. The laser emitted from the first lens is collimated and expanded by the second collimation module. Furthermore, the combination of the liquid lens and the first lens, the second collimation module, and the high-speed scanning galvanometer form a conjugate relationship. Additionally, there is a 4f conjugate relationship between the high-speed scanning galvanometer, the relay lens group, and the objective lens back aperture, thereby enabling scanning imaging and maximizing the use of the focal length variation range of the liquid lens during scanning imaging.

[0062] The signal acquisition module 104 includes an ultrasonic transducer 501 and a data information acquisition unit 502. The ultrasonic transducer 501 receives photoacoustic signals and transmits the photoacoustic signals to the data information acquisition unit 502.

[0063] When the sample, i.e., biological tissue, absorbs the pulsed laser, it generates an ultrasonic signal due to the instantaneous thermoelastic effect. The ultrasonic transducer 501 (UST) receives the ultrasonic signal and then transmits it to the subsequent data acquisition unit 502. After processing and calculation, an image is generated.

[0064] In one specific embodiment, the multi-scale photoacoustic imaging system mainly comprises: a laser emission module 101, a zoom module 102, a laser excitation module 103, and a signal acquisition module 104.

[0065] The specific implementation scheme of laser emitting module 101 is as follows: Figure 3 As shown, laser 201 outputs a 532nm pulsed laser beam. The beam is collimated and expanded by the front convex lens 202 and the rear convex lens 203, so that the diameter of the beam matches the size of the liquid lens 301 used later. The pulsed laser emitted by the laser emitting module 101 is horizontally and without convergence into the zoom module 102.

[0066] The specific implementation scheme of zoom module 102 is as follows: Figure 4a As shown, the laser beam, collimated and expanded by the laser emission module 101, is incident on the liquid lens 301. After applying an external voltage, the liquid lens 301 achieves a certain focusing power, with a refractive power range of -5 to +15. Within the adjustment range of the liquid lens 301, the laser under the objective lens 402 can achieve two excitation modes: optimal focusing on the sample and weak focusing on the sample. The zoom of the liquid lens 301 and the corresponding focusing modes are shown in the figure. Figure 4b As shown. The omnidirectional scanning range can be calculated using geometric optics:

[0067]

[0068] Where M is the magnification from the sample plane to the image plane behind the liquid lens 301, n is the refractive index of the immersion medium, and f 302 and f 301 These are the focal lengths of the cemented doublet lens 302 and the liquid lens 301, respectively. Within the optical power range of the liquid lens 301, we calculated a theoretical total focal length displacement of 36.8 μm. Furthermore, by changing the focal length of the cemented doublet lens 302 and the magnification of the multi-scale photoacoustic imaging system, an appropriate axial scan can be provided, adjusting this total focal length displacement range to approximately 100 μm. This total focal length displacement range corresponds to the displacement between the focal point of the multi-scale photoacoustic imaging system in strong focusing mode and weak focusing mode. After the laser beam exits from the liquid lens 301, it is further collimated and expanded by the third convex lens 303 and the fourth convex lens 304.

[0069] The above-mentioned multi-scale photoacoustic imaging system achieves multi-scale imaging mainly through the following steps:

[0070] (1) After the laser emitting module 101 generates a 532nm pulsed laser, it passes through two convex lenses with appropriate focal lengths (which need to be selected in combination with the size of the objective lens back aperture and the size of the laser emitted by the laser) to generate a light spot that can just fill the objective lens back aperture; (2) The parallel collimated beam from the laser emitting module 101 enters the zoom module 102. By changing the magnitude of the applied voltage, the curvature of the liquid in the liquid lens is changed, and the focal length of the entire system is adjusted accordingly. The size of the light spot at the focal point can also be adjusted within a small range to achieve cross-scale photoacoustic imaging; (3) After the laser is emitted from the zoom module 102, it passes through the reflector, galvanometer and objective lens and is focused on the sample. The sample generates an ultrasonic signal due to the instantaneous thermoelastic effect; (4) The generated ultrasonic signal is received by the signal acquisition module 104 and generated into an image after processing and calculation.

[0071] During operation, the liquid lens 301 is controlled and adjusted. When the laser is optimally focused on the sample, the optical focus is smaller than the acoustic focus, and the image resolution is determined by the laser spot. This is called OR-PAM, with a lateral resolution of 4.92 μm and an imaging depth determined by optics, up to a maximum of 0.7 mm. When the liquid lens 301 is adjusted to weakly focus the laser on the sample, the optical focus is larger than the acoustic focus, and the image resolution is determined by the acoustic spot. This is called AR-PAM, with a lateral resolution of 114.5 μm. Due to the weak focusing, its pulse energy is more than 300 times higher than OR-PAM, and its imaging depth can reach 4.1 mm. This invention is the first high-speed multi-scale system to use the liquid lens 301 to combine OR and AR image features. This system achieves large imaging depth and variable resolution through the electronically controlled high-speed free focus adjustment of the liquid lens 301. The lateral resolution of this system can be continuously switched between 4.9 and 114.5 μm, and the maximum imaging depth can be continuously switched between 0.7 and 4.1 mm.

[0072] Compared with existing technologies, the present invention provides a cross-scale photoacoustic imaging system that uses a zoom module 102 to change the focal length, thereby achieving strong focusing and weak focusing modes on the sample. This allows for switching between optical resolution photoacoustic microscopy (OR-PAM) and acoustic resolution photoacoustic microscopy (AR-PAM) imaging based on a single optical path. When operating as OR-PAM, this cross-scale photoacoustic imaging system can perform imaging at the cellular level; when operating as AR-PAM, it can image structures such as blood vessels and joints at the macroscopic level, thus realizing cross-scale imaging capabilities in the field of photoacoustic imaging. From the overall structure and design of the system, the cross-scale photoacoustic imaging system of the present invention achieves switching between OR-PAM and AR-PAM using a single optical path, rather than combining multiple optical paths together. This eliminates the need for beam splitting and other operations, resulting in a simple, organized, and uncomplicated system. The liquid lens 301 can be electrically controlled for high-speed continuous zoom, thereby achieving continuous adjustment of the system resolution and imaging depth. Furthermore, this multi-scale photoacoustic imaging system has no optical fiber, no beam splitter, and no beam cutter. The entire system has a simple and easy-to-build structure, is not complicated, and has low cost.

[0073] Furthermore, the multi-scale photoacoustic imaging system based on the liquid lens 301 can perform photoacoustic imaging at different depths and scales without changing the positions of the sample and the objective lens 402. Since the curvature of the liquid in the liquid lens 301 is controlled by the magnitude of the applied voltage, the focal plane depth and scale of the entire photoacoustic imaging system can be precisely adjusted within a very small range. It does not require pre-designing the focal length needed for analysis, nor does it require fine-tuning the position of the sample plane, which can greatly improve imaging efficiency and success rate.

[0074] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A multi-scale photoacoustic imaging system, characterized in that, It includes a laser emission module, a zoom module, a laser excitation module, and a signal acquisition module; The laser emitting module is used to emit pulsed lasers; The zoom module achieves at least two focusing modes on the sample by changing the focal length, and the two focusing modes include: a strong focusing mode and a weak focusing mode. The pulsed laser emitted by the laser emitting module passes sequentially through the zoom module and the laser excitation module before irradiating the sample and exciting a photoacoustic signal, which is received by the signal acquisition module. In the strong focusing mode, the cross-scale photoacoustic imaging system is an optical resolution photoacoustic microscopy system; in the weak focusing mode, the cross-scale photoacoustic imaging system is an acoustic resolution photoacoustic microscopy system. The laser excitation module includes a high-speed scanning galvanometer. The laser emitted from the zoom module irradiates the high-speed scanning galvanometer and then enters the objective lens to focus on the sample. The laser excitation module also includes a relay lens group, which consists of two convex lenses with the same focal length and confocal. The back apertures of the high-speed scanning galvanometer, the relay lens group, and the objective lens form a 4f conjugate relationship. The zoom module includes a liquid lens, and the shape of the liquid lens is changed by mechanical pressure, thereby changing the focal length of the liquid lens. The refractive power range of the liquid lens is -5 to +15. The liquid lens includes a lens cavity, the light-emitting side of the lens cavity has an elastic film, and the lens cavity contains an optical liquid. The pressure inside the lens cavity is controlled by injecting or extracting the optical liquid, thereby changing the focal length of the liquid lens. The zoom module also includes a first lens, to which the laser emitted from the liquid lens is incident; the multi-scale photoacoustic imaging system has an omnidirectional scanning range. , Where M is the magnification from the sample plane to the image plane behind the liquid lens, n is the refractive index of the immersion medium in the liquid lens, f1 is the focal length of the first lens, and f 液 It is the focal length of the liquid lens.

2. The multi-scale photoacoustic imaging system as described in claim 1, characterized in that, The laser emitting module includes a laser and a first collimation module. The pulsed laser emitted by the laser is collimated and expanded by the first collimation module and then incident on the zoom module.

3. The multi-scale photoacoustic imaging system as described in claim 1, characterized in that, The signal acquisition module includes an ultrasonic transducer and a data information acquisition unit. The ultrasonic transducer receives the photoacoustic signal and transmits the photoacoustic signal to the data information acquisition unit.

4. The multi-scale photoacoustic imaging system as described in claim 1, characterized in that, The zoom module also includes a second collimation module, through which the laser emitted from the first lens is collimated and then incident on the laser excitation module.

5. A multi-scale photoacoustic imaging system as described in any one of claims 1-3, characterized in that, The liquid lens is an adjustable acoustic gradient lens.

Images