Array scanning photoacoustic microscopic imaging system

Abstract

The invention discloses an array scanning photoacoustic microscopic imaging system, and relates to the technical field of microscopic imaging, and the system comprises a pulse laser which is used for generating pulse laser; the beam shaping device is used for shaping the pulse laser into a pulse laser beam; the lens array is composed of a plurality of lenses, and the lens array is used for focusing the pulse laser beams to form multiple beams of focused light; multiple beams of focused light irradiate a sample to form ultrasonic waves; the ultrasonic transducer is used for converting the ultrasonic waves into ultrasonic signals; and the computer is used for drawing a photoacoustic image according to the ultrasonic signal. The multiple lenses are utilized to form the laser focus array, so that the pulse laser can irradiate multiple positions of the sample at the same time, the small-view-field sub-images scanned by the focuses are synthesized into the large-view-field image through image splicing, and the photoacoustic microscopic imaging time is greatly shortened.

Description

Technical Field

[0001] The present application relates to the field of microscopic imaging technology, and in particular to an array scanning photoacoustic microscopic imaging system. Background Art

[0002] Photoacoustic microscopy (PAM), as a biomedical imaging technology, has significant advantages such as non-destructive, multifunctional and high-resolution. It uses the detected photoacoustic signals to reconstruct images, thereby achieving high-resolution and deep imaging of the structure and function of biological tissues. PAM is playing an increasingly important role in the fields of life sciences, basic medical research and clinical diagnosis. When a pulsed laser is irradiated on biological tissues, the absorbers inside the tissues quickly absorb light energy and produce instantaneous temperature rise, which then expands and releases ultrasonic waves. These ultrasonic waves propagate from the inside of the tissue to the surface and are received by the ultrasonic detector set there. Based on the captured photoacoustic signals, the detector can reconstruct the specific distribution of light energy absorption inside the tissue and form an image.

[0003] PAM technology cleverly combines the advantages of optical imaging and acoustic imaging to provide high-resolution, high-contrast tomographic images of deep tissues. Through PAM imaging, it is possible to avoid the interference of light scattering, break through the "soft limit" of traditional high-resolution optical imaging in depth (about 1 mm), and achieve clear imaging of 50 mm deep in vivo tissues.

[0004] The existing photoacoustic microscopy technology is to focus the laser beam using an objective lens, and the light is transmitted to the biological tissue through the acoustic conductive material in contact with the sample to be imaged, and the sound waves are detected by an ultrasonic transducer. Reconstruction is performed by scanning the laser focus point by point. The lateral resolution is determined by the focus of the laser, which is usually a few microns. At the same time, in order to ensure that the system has optical resolution, the focus scanning step length is smaller than the focus size. In addition, considering the limitation of the repetition frequency of current commercial pulsed lasers, in large field imaging, the scanning imaging time will be an important issue restricting the application of photoacoustic microscopy. Summary of the invention

[0005] The embodiment of the present application provides an array scanning photoacoustic microscopy imaging system to solve the problem of long scanning imaging time in large field of view imaging in the prior art.

[0006] The present application embodiment provides an array scanning photoacoustic microscopy imaging system, comprising:

[0007] Pulse laser, used to generate pulse laser;

[0008] A beam shaping device is arranged downstream of the optical path of the pulsed laser, and the beam shaping device is used to shape the pulsed laser into a pulsed laser beam;

[0009] The lens array is composed of a plurality of lenses, which are arranged in sequence in a plane perpendicular to the pulsed laser beam. The lens array is used to focus the pulsed laser beam to form multiple beams of focused light, and the focus of each lens is different. The multiple beams of focused light are irradiated on the sample to form ultrasonic waves;

[0010] An ultrasonic transducer is arranged near the sample, and is used to convert ultrasonic waves into ultrasonic signals;

[0011] The computer is electrically connected to the ultrasonic transducer, and the computer is used to draw a photoacoustic image according to the ultrasonic signal.

[0012] In a possible implementation, a moving stage is further included, and the sample is placed on the moving stage. When the focused light irradiates the sample, the moving stage drives the sample to move so that the focused light irradiates the entire sample.

[0013] In one possible implementation, the moving stage moves in three-dimensional space perpendicularly and parallel to the focused light.

[0014] In a possible implementation, a water pool is provided on the mobile platform, the sample is placed in the water pool, the water pool is filled with water, and the ultrasonic transducer is immersed in the water.

[0015] In a possible implementation, a data acquisition card is further included, and the data acquisition card is electrically connected between the computer and the ultrasonic transducer.

[0016] In a possible implementation, a controller is also included. The controller is electrically connected to the computer, the pulse laser, the mobile station and the data acquisition card respectively. The controller is started under the control of the computer and controls the pulse laser, the mobile station and the data acquisition card to trigger synchronously.

[0017] In a possible implementation, an amplifier is electrically connected between the data acquisition card and the ultrasonic transducer.

[0018] In a possible implementation, a reflector is disposed between the beam shaping device and the lens array, and the reflector reflects the pulsed laser beam to the lens array at an angle of 90°.

[0019] In a possible implementation, the distance difference between any two focal points and the ultrasonic transducer is greater than the product of the propagation speed of the ultrasonic wave and the pulse width of the pulse laser.

[0020] In a possible implementation, before drawing the photoacoustic image, the computer compensates for the signal intensity difference of the ultrasound signal caused by the position of the ultrasound transducer.

[0021] An array scanning photoacoustic microscopy imaging system in this application has the following advantages:

[0022] High-speed, large-field-of-view photoacoustic microscopy technology based on spatially resolved acoustic signal acquisition. Multiple lenses form a laser focus array, and based on the time delay of the acoustic signals emitted from different focuses to reach the ultrasonic transducer, the acoustic signal generated by each focus is demodulated, and the small-field-of-view sub-images scanned by each focus are synthesized into a large-field-of-view image through image stitching. Finally, digital image processing technology is used to compensate for the difference in acoustic signal intensity introduced by the angle of the ultrasonic transducer, greatly reducing the photoacoustic microscopy time. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0024] Figure 1 A schematic diagram of the composition of an array scanning photoacoustic microscopy imaging system provided in an embodiment of the present application.

[0025] Explanation of the accompanying drawings: 1. lens array; 2. sample; 3. water pool; 4. ultrasonic transducer; 5. moving stage; 6. amplifier; 7. data acquisition card; 8. computer; 9. pulse laser; 10. controller; 11. beam shaping device; 12. reflector. DETAILED DESCRIPTION

[0026] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0027] Figure 1 The present invention provides a schematic diagram of the structure of an array scanning photoacoustic microscopy imaging system. The present invention provides an array scanning photoacoustic microscopy imaging system, including:

[0028] A pulse laser 9, used to generate pulse laser;

[0029] A beam shaping device 11 is arranged downstream of the optical path of the pulse laser 9, and the beam shaping device 11 is used to shape the pulse laser into a pulse laser beam;

[0030] The lens array 1 is composed of a plurality of lenses, which are arranged in sequence in a plane perpendicular to the pulsed laser beam. The lens array 1 is used to focus the pulsed laser beam to form a plurality of focused light beams, and the focus of each lens is different. The plurality of focused light beams are irradiated on the sample 2 to form ultrasonic waves.

[0031] An ultrasonic transducer 4 is arranged near the sample 2, and is used to convert ultrasonic waves into ultrasonic signals;

[0032] The computer 8 is electrically connected to the ultrasonic transducer 4 and is used for drawing a photoacoustic image according to the ultrasonic signal.

[0033] Exemplarily, the function of the beam shaping device 11 is to convert a pulsed laser beam with a smaller beam diameter into a pulsed laser beam with a larger beam diameter by first diverging and then focusing. The energy density of the pulsed laser beam at each point is the same, so that the pulsed laser beam can be irradiated on each lens. The lens array formed by the combination of multiple lenses focuses the pulsed laser beam with a larger beam diameter separately to form multiple focused lights. Each focused light is equivalent to a pulsed laser, and different focused lights are irradiated on different positions of the sample 2, which is equivalent to a pulsed laser beam irradiating different positions of the sample 2 in a scanning manner in multiple times. However, in the present application, multiple focused lights are irradiated on the sample 2 at the same time. Compared with a single pulsed laser beam, when the pulse width of the pulsed laser beam is the same, the efficiency of using multiple focused lights to irradiate the sample 2 at the same time is much higher than that of using a single pulsed laser beam to irradiate the sample 2 in a scanning manner. Therefore, the system of the present application is used for microscopic imaging, which can greatly shorten the imaging time.

[0034] The ultrasonic transducer 4 is close to the sample 2 in an inclined manner, and the number of ultrasonic transducers 4 is one. Since each beam of focused light can generate an ultrasonic wave, an ultrasonic transducer 4 needs to receive multiple ultrasonic waves, but the positions where the ultrasonic waves are generated are different, and the distances between these positions and the ultrasonic transducer 4 are also different. Under such different distances, the attenuation of the ultrasonic waves during propagation is also different. However, when the computer 8 draws the photoacoustic image, the intensity of the ultrasonic signal is a very important indicator. Therefore, in order to eliminate the error in the intensity of the ultrasonic signal caused by the distance, the computer 8 of the present application compensates for the signal intensity difference of the ultrasonic signal caused by the position of the ultrasonic transducer 4 before drawing the photoacoustic image.

[0035] Specifically, multiple groups of ultrasonic propagation experiments of the same intensity at different distances can be conducted in advance, multiple ultrasonic waves are collected by the ultrasonic transducer 4, the intensity of the ultrasonic signal is calculated, and the relationship between the intensity and the distance is analyzed. Then, in actual use, the distance between each focus and the ultrasonic transducer 4 is first measured, and after ultrasonic waves at different positions are collected by the ultrasonic transducer 4, the intensity of the ultrasonic signal corresponding to the ultrasonic wave generated at each position is compensated according to the relationship between the intensity and the distance.

[0036] In the embodiment of the present application, since an ultrasonic transducer 4 needs to collect ultrasonic waves formed by multiple beams of focused light, in order to prevent the ultrasonic waves generated by the focused light at different positions from being simultaneously propagated to the ultrasonic transducer 4 during the duration of the pulsed laser, the present application makes a special setting for the position of the focus. Specifically, the distance difference between any two focal points and the ultrasonic transducer 4 is greater than the product of the propagation speed of the ultrasonic wave and the pulse width of the pulsed laser. With this distance setting, it can be ensured that the ultrasonic waves generated within a complete pulse cycle will not overlap when they reach the ultrasonic transducer 4, that is, after a complete ultrasonic wave is received by the ultrasonic transducer 4, the next ultrasonic wave will arrive.

[0037] In a possible embodiment, a moving stage 5 is further included, and the sample 2 is placed on the moving stage 5 . When the focused light irradiates the sample 2 , the moving stage 5 drives the sample 2 to move, so that the focused light irradiates the entire sample 2 .

[0038] Exemplarily, a three-axis moving mechanism is provided below the moving platform 5, so that the moving platform 5 can move in six degrees of freedom, front and back, left and right, and up and down, respectively, so as to realize the movement of the moving platform 5 in three-dimensional space perpendicular and parallel to the focused light.

[0039] When the moving stage 5 moves in a direction perpendicular to the focused light, the position where the focused light is irradiated on the sample 2 can be adjusted, thereby ensuring that the focused light can irradiate all positions on the sample. When the moving stage 5 moves in a direction parallel to the focused light, the depth of the focus of the focused light on the sample 2 can be adjusted, thereby achieving the drawing of photoacoustic images at different depths of the sample 2.

[0040] Furthermore, a water pool 3 is provided on the moving platform 5 , the sample 2 is placed in the water pool 3 , the water pool 3 is filled with water, and the ultrasonic transducer 4 is immersed in the water.

[0041] Since water absorbs ultrasound waves less than air, water immersion can improve the accuracy of ultrasound waves collected by the ultrasonic transducer 4. At the same time, since the ultrasonic transducer 4 collects ultrasound waves in water, the relationship between the intensity and distance of the ultrasonic signal needs to be analyzed in water during the experiment.

[0042] In a possible embodiment, a data acquisition card 7 is further included, and the data acquisition card 7 is electrically connected between the computer 8 and the ultrasonic transducer 4 .

[0043] Exemplarily, the data acquisition card 7 can convert the ultrasonic signal in analog form into a digital quantity, which can then be recognized by the computer 8 .

[0044] Furthermore, it also includes a controller 10, which is electrically connected to the computer 8, the pulse laser 9, the mobile platform 5 and the data acquisition card 7 respectively. The controller 10 is started under the control of the computer 8, and the controller 10 controls the pulse laser 9, the mobile platform 5 and the data acquisition card 7 to be triggered synchronously.

[0045] The moving path of the mobile stage 5 is pre-designed in the computer 8. By analyzing this pre-determined moving path, it can be determined that the ultrasonic transducer is accurately positioned at the corresponding position on the sample 2 each time it receives an ultrasonic wave. After the computer 8 draws a small field of view sub-image for the ultrasonic signal formed by the ultrasonic wave, it determines the position of the small field of view sub-image in the entire large field of view image. As the ultrasonic transducer 4 continuously receives ultrasonic waves, the computer 8 can continuously generate small field of view sub-images, and splice the already drawn small field of view sub-images based on the positions of the small field of view sub-images to obtain the final large field of view image.

[0046] Furthermore, an amplifier 6 is electrically connected between the data acquisition card 7 and the ultrasonic transducer 4. The amplifier 6 can amplify the tiny ultrasonic signal to a certain extent, thereby ensuring that the analog-to-digital conversion of the data acquisition card 7 is carried out smoothly.

[0047] In a possible embodiment, a reflector 12 is disposed between the beam shaping device 11 and the lens array 1 , and the reflector 12 reflects the pulsed laser beam to the lens array 1 at an angle of 90°.

[0048] For example, the pulsed laser beam is directed to the reflector 12 in a horizontal direction, and the reflector 12 is tilted at an angle of 45° to the horizontal direction, so that the pulsed laser beam can be reflected vertically downward and then irradiated on the lens array 1. By setting the reflector 12, the propagation direction of the light can be changed, thereby achieving the purpose of reducing the volume of the system.

[0049] Although the preferred embodiments of the present application have been described, those skilled in the art may make additional changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications falling within the scope of the present application.

[0050] Obviously, those skilled in the art can make various changes and modifications to the present application without departing from the spirit and scope of the present application. Thus, if these modifications and variations of the present application fall within the scope of the claims of the present application and their equivalents, the present application is also intended to include these modifications and variations.

Claims

1. An array scanning photoacoustic microscopy imaging system, characterized in that: include: A pulse laser (9), used for generating pulse laser; A beam shaping device (11) is arranged downstream of the optical path of the pulse laser (9), and the beam shaping device (11) is used to shape the pulse laser into a pulse laser beam; A lens array (1) is composed of a plurality of lenses, wherein the plurality of lenses are arranged in sequence in a plane perpendicular to the pulsed laser beam, and the lens array (1) is used to focus the pulsed laser beam to form a plurality of focused light beams, wherein the focus of each lens is different; the plurality of focused light beams are irradiated onto a sample (2) to form ultrasonic waves; An ultrasonic transducer (4) is arranged near the sample (2), and the ultrasonic transducer (4) is used to convert the ultrasonic wave into an ultrasonic signal; A computer (8) is electrically connected to the ultrasonic transducer (4), and the computer (8) is used to draw a photoacoustic image based on the ultrasonic signal.

2. The array scanning photoacoustic microscopy imaging system according to claim 1, characterized in that: The invention also comprises a moving stage (5), on which the sample (2) is placed. When the focused light irradiates the sample (2), the moving stage (5) drives the sample (2) to move, so that the focused light irradiates the entire sample (2).

3. The array scanning photoacoustic microscopy imaging system according to claim 2, characterized in that: The moving stage (5) moves in a three-dimensional space perpendicularly and parallel to the focused light.

4. The array scanning photoacoustic microscopy imaging system according to claim 2, characterized in that: A water pool (3) is arranged on the mobile platform (5), the sample (2) is placed in the water pool (3), the water pool (3) is filled with water, and the ultrasonic transducer (4) is immersed in the water.

5. The array scanning photoacoustic microscopy imaging system according to claim 2, characterized in that: It also includes a data acquisition card (7), wherein the data acquisition card (7) is electrically connected between the computer (8) and the ultrasonic transducer (4).

6. The array scanning photoacoustic microscopy imaging system according to claim 5, characterized in that: The invention also comprises a controller (10), wherein the controller (10) is electrically connected to the computer (8), the pulse laser (9), the mobile platform (5) and the data acquisition card (7) respectively, and the controller (10) is started under the control of the computer (8), and the controller (10) controls the pulse laser (9), the mobile platform (5) and the data acquisition card (7) to be triggered synchronously.

7. The array scanning photoacoustic microscopy imaging system according to claim 5, characterized in that: An amplifier (6) is electrically connected between the data acquisition card (7) and the ultrasonic transducer (4).

8. The array scanning photoacoustic microscopy imaging system according to claim 1, characterized in that: A reflector (12) is provided between the beam shaping device (11) and the lens array (1), and the reflector (12) reflects the pulsed laser beam to the lens array (1) at an angle of 90°.

9. The array scanning photoacoustic microscopy imaging system according to claim 1, characterized in that: The distance difference between any two of the focal points and the ultrasonic transducer (4) is greater than the product of the propagation speed of the ultrasonic wave and the pulse width of the pulse laser.

10. The array scanning photoacoustic microscopy imaging system according to claim 1, characterized in that: Before drawing the photoacoustic image, the computer (8) compensates for the signal intensity difference of the ultrasonic signal caused by the position of the ultrasonic transducer (4).

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