A deep extrapolation three-dimensional photoacoustic mesoscopic imaging method

Abstract

The application discloses a three-dimensional photoacoustic mesoscopic imaging method of depth continuation. Firstly, a multi-pitch-angle and multi-angle light source irradiation mode is constructed to realize uniform excitation of biological tissues in different depth ranges. Then, three-dimensional scanning is performed to acquire photoacoustic signals, and a three-dimensional alternating grid scanning mode is designed in one complete scanning to detect photoacoustic signals of deep tissues. Finally, photoacoustic data acquired at different focal depths are combined with corresponding multi-virtual-probe synthetic aperture reconstruction technology to obtain photoacoustic images. The application can finally realize high-resolution and large-depth in high-quality photoacoustic mesoscopic imaging of biological tissues.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of image processing, and particularly relates to a three-dimensional photoacoustic mesoscopic imaging method of depth extension. BACKGROUND

[0002] Photoacoustic imaging is one of the emerging non-invasive medical imaging technologies. When pulsed light irradiates biological tissue, the thermoelastic expansion of the tissue produces ultrasonic waves when it absorbs light energy. The ultrasonic transducer can reconstruct the image of the light absorption distribution characteristics in the biological tissue after receiving the photoacoustic signal. Photoacoustic imaging combines the advantages of high contrast of optical imaging and low scattering of acoustic imaging, and can realize high spatial resolution and high contrast functional and structural imaging. Photoacoustic imaging faces three scales. Among them, photoacoustic macroscopic imaging technology mainly faces large-size biological tissues with a depth greater than 10 mm, such as live animal imaging and human breast functional imaging fields; the depth of photoacoustic microscopic imaging technology is within 1 mm, and it is usually used for cell resolution observation and other fields; photoacoustic mesoscopic imaging technology can realize high-resolution imaging better than 100 microns for shallow (1 to 10 mm) tissues, fill the gap between microscopic (cell) and macroscopic (organ) imaging, and obtain the concentration distribution of oxygenated hemoglobin, deoxygenated hemoglobin and other substances in biological tissues. Therefore, the application has wide application prospects in many fields such as tumor blood vessel imaging, neural imaging, vascular targeted photodynamic therapy and the like.

[0003] In photoacoustic mesoscopic imaging, the excitation light spot is usually only gathered in the tissue at the same depth, and the large numerical aperture spherical focusing ultrasonic transducer used is limited by physical properties, so that the imaging depth and spatial resolution are mutually restricted. The application designs a multi-elevation-angle multi-angle light source excitation mode and a three-dimensional alternating grid scanning mode to realize high-quality photoacoustic mesoscopic imaging with a resolution better than 100 microns when the imaging depth is increased to a centimeter-level depth. In a complete scanning, the three-dimensional alternating grid scanning mode and the multi-elevation-angle multi-angle light source excitation mode are designed to realize the excitation and detection of photoacoustic signals of tissues at different depths. In combination with a synthetic aperture focusing reconstruction algorithm based on multi-focal-depth virtual detection points, high-quality three-dimensional photoacoustic mesoscopic images can be generated in the defocusing area. Through the application, the fine structure and blood flow of blood vessels in the tissue can be captured, and human superficial tissue diseases such as melanoma can be diagnosed, which has great application value in the field of biomedical imaging.

[0004] The high spatial resolution of photoacoustic microscopy in a certain depth is mainly achieved by using high numerical aperture acoustic transducers, but the lateral resolution of the out-of-focus region will decrease rapidly. At present, the image resolution of the out-of-focus region is improved by using different frequency ultrasonic transducers to form an array detection structure and by a synthetic aperture focusing reconstruction technology. In order to improve the imaging quality, the light source illumination mode of photoacoustic microscopy is improved from double-sided same layer illumination to four-sided same layer illumination, which improves the signal-to-noise ratio of the image while maintaining the uniformity of the light.

[0005] At present, the synthetic aperture focusing algorithm has been widely used in ultrasonic image reconstruction or photoacoustic image reconstruction to improve the lateral resolution of the out-of-focus region. The current solutions: one-dimensional synthetic aperture image reconstruction algorithm (Park, J. et al. Delay-multiply-and-sum-based synthetic aperture focusing in photoacoustic microscopy. Journal of Biomedical Optics, 2016, 21(3): 036010) can improve the spatial resolution in one scanning direction; two-dimensional synthetic aperture image reconstruction algorithm (Deng, Z. et al. Two-dimensional synthetic-aperture focusing technique in photoacoustic microscopy. Journal of Applied Physics, 2011, 109(10): 104701) can improve the spatial resolution in two scanning directions; adaptive synthetic aperture image reconstruction algorithm (Deng, Z. et al. Adaptive synthetic-aperture focusing technique for microvasculature imaging using photoacoustic microscopy, Optics Express, 2012, 20(7): 7555-7563) can improve the lateral spatial resolution and signal-to-noise ratio of the reconstructed image in three-dimensional direction, but the resolution and signal-to-noise ratio of the reconstructed image in the far-out-of-focus region are still lower than those in the focal region. The adaptive reconstruction method of photoacoustic microscopy proposed in Chinese patent CN102579073A is based on the existing photoacoustic microscopy technology (US20060184042) to perform synthetic aperture operation on the image in two-dimensional scanning mode, which is limited by the physical performance of the numerical aperture spherical focusing probe itself, and the focal length of the focused region of the image is limited, which limits the improvement of the lateral resolution of the out-of-focus region to some extent.

[0006] Currently, to obtain better quality imaging results, mesoscopic optoacoustic imaging uses multi-side optical fiber bundle to excite light spots to illuminate the same depth tissue layer. The double-sided light mode (Omar, M. et al. Ultrawideband reflection-mode optoacoustic mesoscopy. Optics Letters, 2014, 39(13): 3911-3914) ensures the uniformity of the light spot formed on the surface of the imaging object; in order to improve the image quality, the four-sided light mode (Omar, M. et al. Optical imaging of post-embryonic zebrafish using multi orientation raster scan optoacoustic mesoscopy. Light: Science & Applications, 2017, 6(1): e16186-e16186) can improve the signal-to-noise ratio of the image under the premise of ensuring uniformity. But the above light modes are single angle, and the light spot is focused on the same depth tissue layer, and the information of different depth layers of the tissue cannot be obtained, and to some extent, the information expressed by the image is not complete. The optoacoustic imaging based on the multi-point excitation to form a multi-focus light spot proposed in Chinese patent CN107607473 has limited detection depth, low signal-to-noise ratio, and high measurement cost when realizing global imaging.

[0007] The currently developed optoacoustic mesoscopic imaging method is basically based on a multi-angle tomographic scanning method of an ultrasonic array and a grid scanning method using a single crystal transducer. In order to improve the measurement sensitivity, a spherical focusing single probe scanning mode with a large crystal surface and a large numerical aperture is usually used, but the sensitive area is short, which leads to a significant decline in image resolution outside the focal point, and the imaging depth is usually not more than 3mm. SUMMARY

[0008] In order to overcome the deficiencies of the prior art, the present application provides a deep extension three-dimensional photoacoustic mesoscopic imaging method, first, a multi-pitch angle and multi-angle light source irradiation mode is constructed to realize uniform excitation of biological tissues in different depth ranges; then three-dimensional scanning is performed to obtain photoacoustic signals, and a three-dimensional alternating grid scanning mode is designed in one complete scan to detect photoacoustic signals of deep tissues; finally, photoacoustic data obtained at different focal depths are combined with the corresponding multi-virtual probe point synthetic aperture reconstruction technology to obtain a photoacoustic image. The three-dimensional alternating grid scanning mode can extend the depth range of the sensitive area of the large numerical aperture ultrasonic transducer without additional scanning time cost, and the multi-focal depth virtual probe point synthetic aperture focusing image reconstruction algorithm of the defocusing scanning can reconstruct a high signal-to-noise ratio and high resolution photoacoustic image. The multi-pitch angle and multi-angle light source excitation mode with self-matching and adjustable light source angles can further improve the uniformity of the light source in exciting deep biological tissues. The above scheme features comprehensively improve the quality of photoacoustic mesoscopic imaging of deep tissues.

[0009] The technical scheme adopted by the present application to solve its technical problems is as follows:

[0010] Step 1: Construct a multi-pitch angle and multi-angle light source excitation mode with self-matching and adjustable light source angles to realize uniform excitation of biological tissues in different depth ranges;

[0011] Step 2: Three-dimensional scanning to obtain data, and extending the depth range of the sensitive area of the large numerical aperture ultrasonic transducer through a three-dimensional alternating grid scanning mode to detect photoacoustic signals of deep tissues;

[0012] Step 3: Multi-focal point image reconstruction scheme;

[0013] The multi-focal depth virtual probe point synthetic aperture focusing image reconstruction algorithm of the defocusing scanning is combined with the photoacoustic data obtained at different focal depths to reconstruct a high signal-to-noise ratio and high resolution photoacoustic mesoscopic image.

[0014] Further, the step 1 is specifically:

[0015] The multi-pitch angle and multi-angle light source irradiation forms a light spot focusing area;

[0016] The fiber bundles are placed orthogonally and adjacently, and form a focusing light spot from four directions; the four-arm fiber bundle automatically matches the most suitable angle according to the tissue topography curvature obtained by pre-scanning to form a two-by-two symmetric two-angle placement mode to obtain a light spot focusing area, thereby realizing uniform excitation of biological tissues in different depth ranges.

[0017] Further, the step 2 is specifically:

[0018] Step 2-1: In the photoacoustic mesoscopic imaging method, a small F-number ultrasonic transducer is selected, that is, a large numerical aperture ultrasonic transducer is selected, and the depth of the sensitive area of the ultrasonic transducer is extended through a three-dimensional alternating grid scanning mode.f / α p The value of the ultrasound transducer is less than the set threshold value, wherein α p represents the transducer aperture size, Z f represents the focal length; the focal point is approximated as a point model, the signal sensitivity in the focusing area is improved, the receiving angle of the signal in the defocusing mode is increased, and the depth range of the sensing sensitivity is expanded by three-dimensional alternating grid scanning;

[0019] Step 2-2: The short pulse laser is introduced into the "excitation-detection" coaxial multi-arm optical fiber bundle through the coupling light path, irradiates the target tissue to achieve uniform light intensity distribution; the controller adjusts the three-dimensional translation table to drive the multi-arm optical fiber bundle and the ultrasonic transducer to move, the x direction is continuously moved, the y direction and the z direction are discretely moved, that is, the grid scanning is performed in the xy two-dimensional plane while moving upward or downward along the z direction, and the alternating grid format scanning and collection of the photoacoustic signal in three-dimensional layers are realized.

[0020] Step 2-3: The three-dimensional translation table fixes the grating ruler on the x axis, the y axis and the z axis of the translation table during the alternating grid scanning, to locate and record the photoacoustic signal of each pulse excitation and the coordinates of the current detection point, and simultaneously trigger the collection card to store the photoacoustic signal received by the ultrasonic transducer.

[0021] Further, the step 3 is specifically:

[0022] Step 3-1: Using the "defocusing scanning mode" of the ultrasonic transducer, the focal point is used as a virtual point detector, in the transducer aperture angle range, the photoacoustic signals collected by the adjacent detection points in the three-dimensional alternating grid scanning are weighted back projection, which is expressed by the following formula:

[0023]

[0024] Wherein, P0(x i , y j , t k ) represents the photoacoustic signal intensity of a point k in space after synthesis reconstruction, N represents the total number of multi-focal depth detection points participating in the current point synthesis aperture reconstruction, P(x j′ , y j′ , t k -△t k′ ) represents the actual received photoacoustic signal in space of different detection points, △t k′ represents the time delay of the synthesis reconstruction point to different virtual point detectors; x i′ , y j′ represent the detection position before synthesis reconstruction at t k ; x i , y j represent the detection position after synthesis reconstruction at t k ;

[0025] Step 3-2: Calculate the time delay Δt k′ The formula is:

[0026]

[0027] Where z k represents the z-direction distance from the synthetic reconstruction point k to the ultrasound transducer crystal surface, z f represents the z-direction distance from the virtual point to the ultrasound transducer crystal surface; c represents the propagation speed of the photoacoustic signal in the scanning medium, d k represents the z-direction distance from the synthetic point to the i-th virtual point, d' i represents the Euclidean distance from the synthetic point to the i-th virtual point.

[0028] When Δt k′ < 0, the synthetic point is above the virtual point; when Δt k′ > 0, the synthetic point is below the virtual point.

[0029] Step 3-3: From t k = z k / c, z k = z f + d k , then:

[0030]

[0031] Step 3-4: When performing three-dimensional alternating grid scanning, different z values are obtained at the same probe point in the x and y directions, so there are different z f values, then the multi-focal depth synthetic aperture image reconstruction is described by the following formula:

[0032]

[0033] Where P(x i , y j , t k ) is the photoacoustic signal intensity after multi-focal depth synthetic aperture focusing reconstruction operation; P1(x i′ , y j′ , t k1 - Δt k1′ ) and P2(x i′ , y j′ , t k2 - Δt k2′ ) are the photoacoustic signal intensities at different depth acoustic focal points.

[0034] An electronic device comprises a memory, a processor, and a computer program stored on the memory and executable on the processor, which, when executed by the processor, implements the steps of the deep extrapolation three-dimensional photoacoustic mesoscale imaging method disclosed in the present application.

[0035] A program product comprises a computer program which, when executed, performs the steps of the deep extrapolation three-dimensional photoacoustic mesoscale imaging method disclosed in the present application.

[0036] A storage medium having stored thereon a computer program which, when executed, performs the steps of the deep extrapolation three-dimensional photoacoustic mesoscale imaging method disclosed in the present application.

[0037] The beneficial effects of the present application are as follows:

[0038] The present application can expand the depth range of the sensitive region of a large numerical aperture ultrasonic transducer without additional scanning time cost through a three-dimensional alternating grid scanning mode, and a multi-focal-depth virtual probe point synthetic aperture focusing image reconstruction algorithm combined with defocus scanning can reconstruct a high signal-to-noise ratio, high-resolution photoacoustic image, and a multi-pitch-angle multi-angle light source excitation mode that can be autonomously matched and adjusted in combination with the light source angle can further improve the uniformity of light source excitation of biological tissues at different depths. The present application realizes the improvement of photoacoustic mesoscale imaging quality by comprehensively considering the above-mentioned contents, and can be used for biological tissue imaging and can also detect physiological parameters such as blood oxygen concentration. BRIEF DESCRIPTION OF DRAWINGS

[0039] Figure 1 is a flowchart of the present application;

[0040] Figure 2 is a schematic diagram of a photoacoustic mesoscale imaging measurement platform used in an embodiment of the present application;

[0041] Figure 3 is a schematic diagram of a multi-pitch-angle multi-angle light source excitation mode in an embodiment of the present application;

[0042] Figure 4 is a schematic diagram of the extension of the sensitive region of an ultrasonic transducer in an embodiment of the present application;

[0043] Figure 5 is a schematic diagram of the scanning track topology in an embodiment of the present application;

[0044] Figure 6 is a schematic diagram of a three-dimensional synthetic aperture based on a multi-focal-depth virtual point in an embodiment of the present application;

[0045] Figure 7 is a schematic diagram of a three-dimensional synthetic aperture reconstruction result in an embodiment of the present application. DETAILED DESCRIPTION

[0046] The present invention will be further described below with reference to the accompanying drawings and embodiments.

[0047] This invention improves the detection depth of photoacoustic mesoscopic imaging by employing a multi-elevation-angle, multi-angle light source excitation mode with autonomously adjustable light source angles, combined with a three-dimensional alternating grid scanning method and a corresponding multi-virtual probe point synthetic aperture reconstruction algorithm. The imaging method used in this invention mainly includes a multi-elevation-angle, multi-angle light source device, a photoacoustic signal receiving device, a three-dimensional scanning device, and a data processing and image reconstruction unit. The multi-elevation-angle, multi-angle light source device can autonomously adjust the excitation angle of the light source according to the curvature of the tissue morphology, forming a specific pairwise symmetrical placement pattern with two different angles. The photoacoustic signal receiving device, i.e., an ultrasonic transducer, is used to receive the photoacoustic signals generated by the target object and transmit the signals to the data processing and image reconstruction unit. During the imaging process, the three-dimensional scanning device drives the light source and ultrasonic transducer to perform three-dimensional alternating grid scanning, obtaining photoacoustic signals from multiple depth acoustic focal points. In the defocused area, an image reconstruction within the aperture angle range of the ultrasonic transducer is performed using a multi-depth-of-focus virtual probe point synthetic aperture focusing imaging algorithm, thereby obtaining a high-resolution photoacoustic mesoscopic image.

[0048] This invention employs a three-dimensional alternating grid scanning mode to acquire photoacoustic signals. It utilizes a multi-tilt, multi-angle light source excitation mode with autonomously adjustable light source angles to uniformly excite biological tissues at different depths. Simultaneously, it combines a multi-depth-of-focus virtual probe point synthetic aperture focusing image reconstruction algorithm to reconstruct the photoacoustic signals acquired through the three-dimensional scanning, thereby improving the signal-to-noise ratio and resolution of the photoacoustic mesoscopic image. This invention overcomes the shortcomings of existing methods in terms of photoacoustic signal excitation and detection depth, improving the quality of photoacoustic mesoscopic imaging. Based on the three-dimensional alternating grid scanning mode, it expands the depth range of the sensitive area of ​​the large numerical aperture ultrasonic transducer, detecting photoacoustic signals from tissues at different depths. The multi-tilt, multi-angle light source excitation mode with autonomously adjustable light source angles focuses light into a specific depth region within the tissue, providing uniform illumination with sufficient energy density, thus exciting biological tissues at different depths to generate photoacoustic signals. The three-dimensional photoacoustic mesoscopic image reconstruction method based on the multi-depth-of-focus virtual probe point synthetic aperture focusing imaging algorithm reconstructs high signal-to-noise ratio and high-resolution photoacoustic mesoscopic images.

[0049] like Figure 1 As shown, a depth-extended three-dimensional photoacoustic mesoscopic imaging method includes:

[0050] S1: Multi-tilt and multi-angle light source excitation mode with adjustable light source angle to achieve uniform excitation of biological tissues at different depths;

[0051] S2: three-dimensional scanning obtains data, and a three-dimensional alternate grid scanning mode is used to expand the depth range of a large numerical aperture ultrasonic transducer sensitive area, and a photoacoustic signal of a deep tissue is detected;

[0052] S3: a multi-focus image reconstruction scheme is used to reconstruct a high signal-to-noise ratio and high resolution photoacoustic mesoscopic image by using a multi-focus depth virtual detection point synthetic aperture focusing image reconstruction algorithm to reconstruct the photoacoustic data obtained at different focus depths.

[0053] The S1 comprises:

[0054] S11: the light source module is designed as a multi-elevation angle and multi-angle light source excitation mode, so as to form a certain depth range of a light spot focusing area. The two-by-two orthogonal and adjacent optical fiber bundles are used to form a focusing light spot from four directions. Firstly, a pre-scanning is performed to obtain a tissue topography curvature. Then, according to the tissue topography curvature, the four-arm optical fiber bundle is automatically adjusted to match the most suitable angle, and a specific two-by-two symmetric two-angle placement mode is formed to obtain the light spot focusing area, so that the biological tissues in different depth ranges are uniformly excited.

[0055] The S2 comprises:

[0056] S21: the ultrasonic transducer used in the photoacoustic mesoscopic imaging method is an ultrasonic transducer with strong focusing performance (F-number, that is, Z f / α p , and the value of α p represents the transducer aperture size, Z f represents the focal length, the transducer with a small F-number is selected, the focus point is approximately a point model, the signal sensitivity in the focusing area is improved, the receiving angle of the signal in the off-focus mode is increased, but at this time, the focusing high sensitivity signal area is reduced, and therefore the depth range of the sensing sensitivity is expanded by using the three-dimensional alternate grid scanning mode;

[0057] S22: a short pulse laser is introduced into a multi-arm optical fiber bundle in a "excitation-detection" coaxial mode through a coupling light path, the target tissue is irradiated to realize uniform light intensity distribution, a controller adjusts a three-dimensional translation table to drive the multi-arm optical fiber bundle and the ultrasonic transducer to move, the x direction is continuously moved, the y direction and the z direction are discretely moved, that is, the grid scanning is performed in the xy two-dimensional plane, and the three-dimensional layer photoacoustic signal is alternately scanned and collected.

[0058] S23: the three-dimensional translation table fixes the grating ruler on the x axis, the y axis and the z axis of the translation table during the alternate grid scanning, and is used to locate and record the photoacoustic signal of each pulse excitation and the coordinate of the current detection point, and simultaneously triggers the collection card to store the photoacoustic signal received by the ultrasonic transducer.

[0059] The S3 comprises:

[0060] S31: using the "off-focus scanning mode" of the ultrasonic transducer, taking its focal point as a virtual point detector, in the transducer aperture angle range, the photoacoustic signals collected at adjacent probe points in the three-dimensional alternating grid scanning are weighted back projection, which can be expressed by the following formula:

[0061]

[0062] S32: calculate the time delay Δt k′ The formula is

[0063] When Δt k′ < 0, the synthetic point is above the virtual point, when Δt k′ > 0, the synthetic point is below the virtual point.

[0064] S33: t k = z k / c, z k = z f + d k , then:

[0065]

[0066] S34: when performing three-dimensional alternating grid scanning, different z values can be obtained at the same probe point in the x direction and y direction, so that different z f values, then the multi-focus depth synthetic aperture image reconstruction can be described by the following formula:

[0067]

[0068] S35: in the three-dimensional alternating grid scanning scheme provided in this embodiment, the z direction has two focal points, namely

[0069]

[0070] Wherein:

[0071]

[0072] Embodiment:

[0073] Referring to Figure 2 , it is a photoacoustic mesoscopic imaging measurement platform used for collecting three-dimensional photoacoustic data in the embodiment of the application, and the specific steps of obtaining three-dimensional alternating grid scanning data are as follows:

[0074] 1) Put the biological sample above the imaging platform, and smear ultrasonic coupling liquid on the surface of the sample, adjust the height of the sample by the lifting platform so that the sample is located below the open imaging window of the coupling water tank center containing deionized water (used for coupling acoustic signal to reduce attenuation) and closely contacts with the film, and the biological sample used in the embodiment is a mouse;

[0075] 2) Based on the multi-pitch angle multi-angle light source excitation mode, the short pulse laser is uniformly irradiated on the surface of the imaging object (the surface of the back of the mouse) from the top of the sample side through the multi-arm optical fiber;

[0076] 3) Adjust the height of the sample and the ultrasonic transducer, immerse the ultrasonic transducer and the optical fiber head in water, and make the detection crystal surface of the ultrasonic transducer be about 5mm away from the surface of the sample, and the calibration focal length of the ultrasonic transducer in the embodiment is 5mm;

[0077] 4) Set the starting point, scanning range, x-axis scanning length, y scanning length axis, z-axis scanning length, x-axis moving speed, y-axis and z-axis step length, single point collection number and collection frequency of the three-dimensional alternate grid scanning in the control program;

[0078] 5) When the industrial computer sends a start collection instruction, the ultrasonic transducer and the multi-arm optical fiber bundle driven by the translation table start moving along the x-axis, y-axis and z-axis directions preset by the program, at this time, the grating ruler records the distance and direction of the movement of the translation table, and at the same time, the collection card is triggered to record the photoacoustic signals received by the transducer, and the signals are stored into the computer after being processed by the amplifier.

[0079] Figure 3 It is a multi-pitch angle multi-angle light source excitation mode schematic diagram in the embodiment of the application, the four-arm optical fiber bundle can automatically match the most suitable angle, in the embodiment, the light source angle is set as follows:

[0080] The optical fiber bundles are orthogonally placed in pairs and irradiated from four directions to form a focused light spot. The four-arm optical fiber bundle automatically matches the most suitable angle according to the curvature of the tissue topography, forms a two-by-two symmetric two-angle placement mode (that is Figure 3 The optical fiber bundle 1 and the optical fiber bundle 2 are symmetrically arranged at the same angle, and the optical fiber bundle 3 and the optical fiber bundle 4 are symmetrically arranged at another same angle), a light spot focusing area is obtained, and uniform excitation of biological tissues in different depth ranges is realized.

[0081] Figure 4 It is an ultrasonic transducer sensitive area extension mode schematic diagram in the embodiment of the application, and the ultrasonic transducer can extend the focusing depth of the reconstructed image when moving in the z direction of the translation table.

[0082] Figure 5 It is a scanning track schematic diagram of the ultrasonic transducer in the three-dimensional alternate grid scanning mode in the embodiment of the application, and in the embodiment, the scanning is set as follows:

[0083] The moving speed of x axis is 1 mm / s, the scanning step of y axis is 100 μm, the scanning step of z axis is 100 μm, the collection point number is 10 points / s, the used laser wavelength is 750 nm, and the scanning starting position is from the lower left. The ultrasonic transducer moves at a constant speed along the program in the x positive direction in the xy plane to the predetermined scanning length, then steps 100 μm in the y positive direction in the xy plane, then steps 100 μm in the z direction, and then moves at a constant speed in the x negative direction from the xy plane to the same position as the starting x coordinate, that is, the ultrasonic transducer moves along the trajectory as shown in the figure until the scanning ends. Figure 5

[0084] Figure 6 is a three-dimensional synthetic aperture schematic diagram based on multi-focal depth virtual point detection in the embodiment of the application, and the specific operation steps are as follows:

[0085] 1) The maximum value projection is performed on the collected photoacoustic mesoscopic imaging data by using a data processing tool, the three-dimensional information of the image is obtained, and the characteristic information of the image is obtained according to the three-dimensional cross-sectional projection result;

[0086] 2) Different z values can be obtained from the three-dimensional alternating grid scanning, so that different z f values are obtained, and the synthetic point k is selected according to the three-dimensional cross-sectional projection result obtained in step 1), that is, the following can be calculated:

[0087] wherein the sound speed c in water is assumed to be 1500 m / s;

[0088] 3) The calculated t k1 -△t k1′ , t k2 -△t k2′ is substituted into the following formula, and the reconstructed photoacoustic signal intensity P(x i , y j , t k ) can be obtained:

[0089]

[0090] Figure 7 is a three-dimensional synthetic aperture reconstruction result based on multi-focal depth virtual points in the embodiment of the application, and the result in the embodiment shows that the blood vessel structure is missing after two-dimensional scanning reconstruction, and the blood vessel structure is complete after three-dimensional scanning reconstruction (the method of the patent).​

Claims

1. A method of depth-extended three-dimensional photoacoustic mesoscale imaging, comprising: It comprises the following steps: Step 1: Constructing a multi-elevation-angle multi-angle light source excitation mode with self-matching angle adjustment of light source, realizing uniform excitation of biological tissues in different depth ranges; Multi-elevation-angle multi-angle light source irradiation forms a light spot focusing area; The fiber bundles are placed orthogonally and adjacently, and form a focused light spot from four directions; the four-arm fiber bundle automatically matches the most suitable angle according to the tissue topography curvature obtained by pre-scanning, forms a two-symmetrical two-angle placement mode, obtains a light spot focusing area, and realizes uniform excitation of biological tissues in different depth ranges; Step 2: Three-dimensional scanning to obtain data, through a three-dimensional alternating grid scanning mode, the depth range of the sensitive area of a large numerical aperture ultrasonic transducer is expanded, and the photoacoustic signal of deep tissue is detected; Step 3: Multi-focus image reconstruction scheme; The photoacoustic data obtained at different focal depths are reconstructed into high signal-to-noise ratio and high resolution photoacoustic mesoscopic images by a multi-focus depth virtual probe synthetic aperture focusing image reconstruction algorithm.

2. The method of claim 1, wherein, The step 2 is specifically: Step 2-1: In the photoacoustic mesoscopic imaging method, an ultrasonic transducer with a small F-number is selected, that is , wherein represents the transducer aperture size, represents the focal length; the focal point is approximated as a point model, the signal sensitivity in the focusing area is improved, the receiving angle of the signal in the defocusing mode is increased, and the depth range of the sensing sensitivity is expanded through three-dimensional alternating grid scanning; Step 2-2: short pulse laser is introduced into the "excitation-detection" coaxial multi-arm fiber bundle through the coupling light path, irradiates the target tissue to achieve uniform light intensity distribution; the controller adjusts the three-dimensional translation table to drive the multi-arm fiber bundle and the ultrasonic transducer to move, x a continuous motion in the direction, y a continuous motion in the direction and z a discrete motion in the direction, namely, xy a grid scanning in the two-dimensional plane while moving upward or downward in the direction, z a three-dimensional layer of photoacoustic signals is alternately scanned and collected in a grid format. Step 2-3: The three-dimensional translation stage fixes the grating ruler on the translation stage at the alternate grid scanning x axis, y axis and z axis to position and record the photoacoustic signal of each time pulse excitation and the coordinate of the current detection point, and trigger the acquisition card to store the photoacoustic signal received by the ultrasonic transducer.

3. The method of claim 1, wherein, The step 3 is specifically: Step 3-1: Using the "off-focus scanning mode" of the ultrasonic transducer, taking its focal point as a virtual point detector, within the transducer aperture angle range, the photoacoustic signals collected by adjacent probes in the three-dimensional alternating grid scanning are weighted back projection, which is expressed by the following formula: wherein, represents a point in space k synthetically reconstructs the photoacoustic signal intensity, represents the total number of multi-focal depth probe sites participating in the synthetic aperture reconstruction of the current point, represents the photoacoustic signal actually received in space by different probe sites, represents the time delay of the synthetically reconstructed point to different virtual point detectors; , represents the probe position before the synthetic reconstruction at ; represents the probe position after the synthetic reconstruction at ; Step 3-2: Calculate the time delay The formula is: ； wherein represents a synthetic reconstruction point k to the ultrasound transducer facet z direction distance, represents a virtual point to the ultrasound transducer facet z direction distance; c represents a speed of propagation of the photoacoustic signal in the scanned medium, represents a synthetic point distance to the i first virtual point z direction distance, represents a synthetic point distance to the i first virtual point When the synthetic point is above the virtual point; when the synthetic point is below the virtual point; Step 3-3: from , then: Step 3-4: When the three-dimensional alternate grid scanning is performed, different values of the x direction, y direction are obtained at the same probe site, so different values of the z direction are obtained, and different values of the direction are obtained, then the multi-focal depth synthetic aperture image reconstruction is performed using the following formula: wherein is the photoacoustic signal intensity after the multi-focal depth synthetic aperture focusing reconstruction operation; and is the photoacoustic signal intensity at the different depth acoustic focal points; , .

4. An electronic device, comprising: A computer program product comprising a memory, a processor and a computer program stored on the memory and executable on the processor, the computer program being executed by the processor to implement the steps of the method according to any one of claims 1-3.

5. A program product, characterized by A computer program product comprising a computer program which, when executed, is arranged to perform the steps of the method according to any one of claims 1-3.

6. A storage medium, characterized by A computer program product comprising a computer program which, when executed, is arranged to perform the steps of the method according to any one of claims 1-3. A computer program product comprising a computer program which, when executed, is arranged to perform the steps of the method according to any one of claims 1-3.

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