Photoacoustic calculation mesoscopic imaging device and method based on linear light scanning

Abstract

The invention discloses a photoacoustic calculation mesoscopic imaging device and method based on linear light scanning. According to the invention, NIR (near infrared) focusing line light scanning, low-frequency annular array detection and composite image calculation and reconstruction are fused. The near-infrared light which is subjected to multi-angle scanning and highly focused in the whole imaging area keeps the fine optical resolution capability in the direction perpendicular to the length direction of the linear light, and efficient photoacoustic signal excitation is achieved. By adopting the low-frequency annular ultrasonic transducer array, high-sensitivity full-view detection of low-attenuation photoacoustic signals is ensured, and the defect of insufficient near-infrared optical absorption is remarkably compensated. Through composite image calculation and reconstruction, the acoustic diffraction limit of the low-frequency photoacoustic signal in the line light length direction is broken through, and background noise with artifacts is suppressed. The technology provides a new visual angle with high spatial resolution for non-invasive and label-free deep small animal brain imaging.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of medical mesoscopic imaging, and particularly relates to a photoacoustic computed mesoscopic imaging device and method based on line light scanning. BACKGROUND

[0002] In preclinical studies, there is an urgent need for a non-invasive long-term imaging technique for small animal brains that can maintain the integrity of the scalp and skull, in order to maintain the original physiological state and monitor the progression of chronic diseases. Abnormal hemodynamic phenomena such as angiogenesis, changes in cerebral blood volume and blood flow, and fluctuations in blood oxygen are associated with various disease states, including brain tumors, stroke, and neurodegenerative diseases. Unfortunately, the complex brain structure (such as the scalp, skull, and dense blood vessel system) leads to refractive index mismatch and high optical attenuation, which limits the performance of optical imaging. To solve these problems, invasive surgery including scalp removal, skull thinning, and skull window implantation is usually used to improve the quality of optical imaging. However, these surgeries can have potential side effects, including mechanical stress during the surgery, thermal stimulation, and changes in intracranial pressure after the surgery.

[0003] To solve the inherent difficulties of non-invasive brain imaging, in the method of optical imaging, NIR-II fluorescence imaging can provide high spatiotemporal resolution and high tissue penetration capability through exogenous contrast agents and wide-field illumination. However, the applicability of long-term monitoring is limited by fluorescence bleaching and metabolic clearance. In the method of acoustic imaging, ultrasound localization microscopy achieves high spatial resolution imaging of the transcranial whole-brain vascular network by analyzing the echo phase, amplitude, and time delay generated by exogenous microbubbles. However, due to the limitations of technical stability and complexity, the scalp needs to be removed, and repeated injection of microbubbles is required. Photoacoustic Computed Tomography (PACT) is a high-resolution hybrid imaging technique that can preserve the integrity of the scalp and skull to achieve sub-millimeter resolution. However, the complex brain structure significantly attenuates high-frequency ultrasound waves, which fundamentally limits the spatial resolution. Therefore, there is an urgent need to develop a non-invasive, label-free visualization imaging method with micron-level spatial resolution for the vascular structure in the intact small animal brain. SUMMARY

[0004] (I) Technical problems to be solved The problems to be solved by the present application include: the limitation of the optical and acoustic attenuation of the scalp, skull and brain tissue objectively existing in small animal brain imaging on the imaging effect, the traditional optical and acoustic imaging means cannot realize high spatial resolution imaging under the premise of non-invasive and label-free; in the existing photoacoustic imaging mode, using a low-frequency ultrasonic transducer to detect low-frequency photoacoustic signals can reduce acoustic attenuation, but cannot realize label-free high spatial resolution imaging; NIR laser can effectively increase the optical penetration depth, however, with the increase of the wavelength of the laser, the optical absorption coefficient of endogenous absorbers such as hemoglobin is greatly attenuated, and the existing photoacoustic imaging means cannot guarantee the imaging sensitivity and signal-to-noise ratio while guaranteeing the imaging resolution.

[0005] The present application combines NIR line light scanning, low-frequency ring array acoustic detection and composite calculation image reconstruction, and proposes a photoacoustic computed mesoscopy (PACMes) technology. The technology can realize high sensitivity and high spatial resolution non-invasive and label-free small animal brain imaging. The deep penetration characteristics of NIR laser, the high resolution of the focusing direction of line light and the high sensitivity of the detection of low-frequency ultrasonic excitation in the length direction of line light are used, and through multi-angle full-view scanning, combined with a reconstruction algorithm, an isotropic high optical resolution image is obtained.

[0006] (II) Technical scheme To solve the technical problems, the present application provides a photoacoustic computed mesoscopy device and method based on line light scanning, and the specific technical scheme is as follows.

[0007] A photoacoustic computed mesoscopy device based on line light scanning, comprising a light source assembly, a light path modulation assembly, a line light scanning assembly, an array ultrasonic acquisition system assembly and a computer; The light source assembly comprises a NIR nanosecond pulse laser and a function generator, wherein the NIR nanosecond pulse laser is electrically connected with the function generator, the NIR pulse laser emitted by the NIR nanosecond pulse laser enters the line light scanning assembly after passing through the light path modulation assembly; the function generator is used for synchronizing laser pulse, scanning control and data acquisition; The light path modulation assembly comprises a lens group and a hexagonal homogenizing rod, which is used for improving the divergence angle of the NIR pulse laser and shaping and homogenizing the light spot to obtain a circular nearly flat top light; The line light scanning assembly comprises an elliptical light spot modulation assembly, a scanning system assembly and a line light modulation assembly; the elliptical light spot modulation assembly comprises a plug-in mirror, a variable diaphragm, a plano-convex and plano-concave lens group and a cylindrical lens group, which are used to generate an elliptical light spot corresponding to the line light required by the field of view resolution and imaging depth, wherein the plug-in mirror is used to switch different light paths according to different imaging needs; the scanning system assembly comprises an electric rotary displacement table and a two-dimensional galvanometer system, wherein the electric rotary displacement table is used to mount the cylindrical lens group to obtain the required angle of the line light by coaxial rotation, and the two-dimensional galvanometer system is used to scan the line light at a specific angle, both of which are connected with the function generator of the light source assembly to ensure synchronous control; the line light modulation assembly comprises a 4-f double-cemented lens combination, an objective lens, a detachable objective lens switching device and an f-theta lens, which are used to generate the line light required for imaging, and the focal plane of the objective lens is arranged to be coplanar with the focal plane of the f-theta lens. The array ultrasonic acquisition system assembly comprises a line-focusing low-frequency ultrasonic annular array, a multi-channel high-sampling-rate data acquisition system, an elastic light-transmitting and sound-transmitting film and a translation lifting table; wherein the acoustic focal zone of the ultrasonic annular array is arranged to be coplanar with the optical focal zone of the f-theta lens of the line light modulation assembly, so as to improve the ultrasonic acquisition sensitivity; the ultrasonic annular array is electrically connected with the data acquisition system, wherein the data acquisition system integrates a signal amplifier and a data acquisition card, which are used to acquire photoacoustic data; the elastic light-transmitting and sound-transmitting film is installed at the bottom of the ultrasonic annular array, which is used to separate the pure water for coupling between the imaging object and the annular array; and the translation lifting table is used to fix the imaging object and adjust the imaging surface to the acoustic and optical focal planes. The computer is used to control the scanning operation and data acquisition and storage of the photoacoustic computational mesoscopic imaging device.

[0008] Preferably, the light source assembly and the light path modulation assembly work as follows: the NIR pulsed laser emitted by the NIR nanosecond pulsed laser passes through a plano-convex lens and is focused to the end face of a hexagonal homogenizing rod, the focal point is located inside the cavity of the hexagonal homogenizing rod, and then passes through another plano-convex lens to collimate, so as to obtain a circular near-flat-top light spot after divergence angle improvement and shaping, and the light spot is guided to the subsequent light path.

[0009] Preferably, the line light scanning assembly directs the circular near-flat-top light beam into two light paths through the plug-in mirror according to the field of view resolution and imaging depth required by imaging, and the two light paths are respectively for different field of view resolution requirements.

[0010] Preferably, the first path of the two optical paths is a large field of view deep penetration depth optical path, the variable aperture changes the spot size while optimizing the spot edge quality, the circular collimated spot is modulated into a short axis focusing elliptical spot by the cylindrical lens group, where the long axis length is consistent with the nominal effective entrance pupil of the f-theta lens and remains collimated, and the short axis direction focusing focal point coincides with the f-theta lens entrance pupil; the required line light is obtained on the f-theta lens optical focal plane by reflecting the two-dimensional galvanometer system into the f-theta lens entrance pupil, and the line light angle is changed by rotating the cylindrical lens group along the optical axis direction by the electric rotary displacement stage, and the line light is scanned on the two-dimensional focal plane along the line light focusing direction by the coordinated rotation of the two mirrors of the two-dimensional galvanometer system.

[0011] Preferably, the second path of the two optical paths is a small field of view high resolution optical path, the variable aperture first preliminarily changes the spot size while optimizing the spot edge quality, and then changes the spot size in a large range by the plano-convex plano-concave lens group, the circular collimated spot is modulated into a specific size collimated elliptical spot by the cylindrical lens group, the long axis length is ensured to be consistent with the corresponding nominal effective entrance pupil of the objective lens by switching the plano-concave lens, the required line light is obtained on the objective lens optical focal plane by reflecting the two-dimensional galvanometer system and the 4-f double cemented lens combination into the corresponding objective lens entrance pupil, and the line light angle is changed by rotating the cylindrical lens group along the optical axis direction by the electric rotary displacement stage, and the line light is scanned on the two-dimensional focal plane along the line light focusing direction by the coordinated rotation of the two mirrors of the two-dimensional galvanometer system.

[0012] Preferably, the line light scanning assembly works as follows: the electric rotary displacement stage and the two-dimensional galvanometer system work cooperatively, the electric rotary displacement stage is rotated to each fixed angle, and the two-dimensional galvanometer system performs one full field of view scan, the scan direction is parallel to the line light focusing direction, the scan step length is determined by the line light focusing direction width, and meets the dense sampling standard, and the scan range is a square circumscribed to the required imaging circular field of view; a suitable number K of angles is selected according to the imaging field of view and the line light focusing direction width, the number of elements of the ring array is N, and the number of scanned line lights at each angle is the scan range width divided by the scan step length, denoted as M.

[0013] Preferably, the array ultrasonic acquisition system assembly and the computer work as follows: the photoacoustic signal excited by each line light is converted into a one-dimensional time-intensity sequence signal array by the acquisition system, the array length is denoted as A, which is set by the acquisition card acquisition frequency and the laser pulse repetition frequency, and the acquisition card simultaneously acquires all the element data NxA; the MxNxA data acquired at each line light scanning angle is stored once on the computer, and the buffer is emptied for the next angle data acquisition; the final photoacoustic data acquired is stored and processed by the computer, and the data storage form is a four-dimensional matrix KxMxNx A.

[0014] The application also discloses a photoacoustic computed mesoscopic imaging method based on line light scanning, which adopts the photoacoustic computed mesoscopic imaging device based on line light scanning to obtain non-destructive mesoscopic imaging of a target object, and steps are as follows: Step S1, fixing the imaging target object on the translation lifting platform, slowly moving the imaging surface position to the sound and light coincident focal plane, so that the elastic light-transmitting and sound-transmitting film is closely attached to the imaging object, and the subject is continuously anesthetized by the gas anesthesia machine during the living body imaging process; Step S2, adding pure water to the ultrasonic annular array to fill the entire array cavity; Step S3, according to the required field of view resolution and imaging depth, selecting the corresponding optical path by using the insertion type reflector, presetting the line light angle number K, calculating the number M of single-angle scanning line lights according to the line light scanning range and scanning step length, the line light scanning direction being the line light focusing direction, and planning the two-axis enabling voltages of the two-axis galvanometer system corresponding to the two-dimensional parameters of the specific positions of the M line lights at each line light angle; Step S4, the computer controls the electric rotary displacement table to rotate to the first preset angle and enables the fixation, triggers the NIR nanosecond pulse laser to emit the NIR pulse laser, synchronously enables the two-axis galvanometer system to the first line light position, obtains the line light on the imaging surface through the optical path modulation assembly and the line light scanning assembly, the first laser pulse corresponds to the excited first photoacoustic time sequence signal which is collected by the array ultrasonic acquisition system assembly, and a 1×1×N×A matrix is stored in the computer in real time; through the two-axis rotation of the two-axis galvanometer system, the line light is scanned to the second line light position, the second laser pulse corresponds to the excited second photoacoustic time sequence signal which is collected by the array ultrasonic acquisition system assembly, and a 1×1×N×A matrix is stored in the computer in real time; when the line light is scanned to the Mth line light position, a 1×M×N×A matrix composed of all the photoacoustic signals corresponding to the first line light angle is obtained; Step S5, the electric rotary displacement table is controlled to rotate to the next preset angle and is enabled to be fixed, the NIR nanosecond pulse laser is triggered, and step S4 is repeated to start the full field of view scanning at the next angle; Step S6, step S5 is repeated until the total rotation angle of the electric rotary displacement table covers 180°, and the data acquisition of all line light angles is completed, and a corresponding K×M×N×A photoacoustic signal matrix is obtained in the computer; Step S7, based on the obtained photoacoustic signal matrix, the target object is reconstructed to obtain a non-destructive brain mesoscopic imaging result.

[0015] Preferably, in step S7, the reconstruction is performed by using the following formula:

[0016] wherein, is the initial sound pressure generated by the pulsed laser radiation target object, is the linear light focusing direction, is the sound velocity, is the two-dimensional spatial position of the annular array element, t is the time of flight of the generated photoacoustic signal, and C is a thermodynamic constant parameter, is the photoacoustic signal sequence collected at the angle, is the integral time window, which is determined by the linear light focusing direction width and the sampling rate of the collection system.

[0017] (Three) beneficial effects Compared with the prior art, the present application has significant technical effects, and the beneficial effects can be embodied from at least the following aspects: (1) The present application discloses that the high-sensitivity deep-layer photoacoustic imaging is realized by exciting a photoacoustic signal with an NIR laser and a low-frequency annular ultrasonic transducer. The conventional photoacoustic brain microscopic imaging system uses a visible light band laser to excite a blood vessel photoacoustic signal, and uses the characteristics of high absorption coefficients of oxygenated hemoglobin and deoxygenated hemoglobin in the visible light band to realize high-contrast brain blood vessel network imaging, but the optical attenuation coefficient in the visible light band limits the effective penetration depth. Using the NIR band can increase the effective penetration depth, but the optical absorption coefficients of oxygenated hemoglobin and deoxygenated hemoglobin are both relatively serious. The present application uses top NIR laser excitation to increase the effective imaging depth, and low-frequency ultrasonic array lateral detection to improve the detection sensitivity. Since weak optical absorption can produce a large penetration depth, an excitation region extending along the beam axis is formed, and a lateral propagation cylindrical ultrasonic wave is thus generated, so that the use of lateral detection can better improve the weak optical excitation detection sensitivity.

[0018] (2) The present application discloses that the multi-angle linear light scanning and computational reconstruction break through the limitation of the acoustic diffraction limit on the imaging resolution in photoacoustic computed tomography. The conventional photoacoustic computation reconstruction needs to use a high-frequency long-bandwidth ultrasonic transducer to optimize the imaging resolution, however, the biological tissue has a large attenuation to high-frequency ultrasonic, and the sensitivity of the high-frequency ultrasonic transducer is poor, so that the conventional photoacoustic computed brain imaging needs to make a trade-off between the resolution and the imaging depth. The present application uses the advantage of the optical resolution in the width direction of the linear light focusing to realize isotropic spatial resolution through computational reconstruction, and successfully combines the characteristics of low-frequency ultrasonic high sensitivity and deep penetration while ensuring the imaging resolution.

[0019] (3) The present application discloses that the combination of NIR linear light scanning, low-frequency annular array acoustic detection and composite computational image reconstruction realizes high-resolution, high-penetration depth and high-sensitivity non-invasive long-term in-vivo imaging. In preclinical research, non-invasive, non-labeled long-term monitoring of small animal brain blood vessel network can be realized. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1The schematic diagram of a photoacoustic computed mesoscopic imaging system based on line light scanning according to the present application.

[0021] Figure 2 The schematic diagram of a composite computed image reconstruction principle according to the present application.

[0022] Figure 3 The effect comparison diagram of the present application and traditional photoacoustic imaging technology.

[0023] In the figure, corresponding technical terms and their reference numerals are as follows: NIR nanosecond pulsed laser 1-1, function generator 1-2, plano-convex lens 2-1, hexagonal homogenizing rod 2-2, plano-convex lens 2-3, plug-in mirror 3-1, mirror 3-2, adjustable diaphragm 3-3, cylindrical lens group mounted on a motorized rotary displacement table 3-4, two-dimensional large-beam galvanometer system 3-5, f-theta lens 3-6, control system 3-7, adjustable diaphragm 4-1, plano-convex lens 4-2, movable plano-concave lens 4-3, movable plano-concave lens 4-4, cylindrical lens group mounted on a motorized rotary displacement table 4-5, two-dimensional galvanometer system 4-6, double cemented lens 4-7, double cemented lens 4-8, mirror 4-9, reversible mirror 4-10, movable objective lens group 4-11, annular ultrasonic array system 5-1, acquisition system 5-2, computer 6. DETAILED DESCRIPTION

[0024] The present application proposes a photoacoustic computed mesoscopic imaging device and method based on line light scanning to solve the technical problem. The technical solution of the present application is further illustrated by specific embodiments in combination with the accompanying drawings.

[0025] The present application proposes a photoacoustic computed mesoscopic imaging system based on line light scanning, specifically as shown in the figure, Figure 1 The system includes a light source assembly, a light path modulation assembly, a line light scanning assembly, an array ultrasonic acquisition system assembly, and a computer.

[0026] As shown in the figure, Figure 1 The light source assembly includes a NIR nanosecond pulsed laser 1-1 and a function generator 1-2.

[0027] As shown in the figure, Figure 1 The light path modulation assembly includes a plano-convex lens 2-1, a hexagonal homogenizing rod 2-2, and a plano-convex lens 2-3.

[0028] As shown in the figure, Figure 1As shown, the line light scanning assembly includes a strip-in mirror 3-1, a mirror 3-2, an adjustable diaphragm 3-3, a cylindrical lens group 3-4 mounted on a motorized rotary displacement stage, a two-dimensional large-beam galvanometer system 3-5, an f-theta lens 3-6, a control system 3-7, an adjustable diaphragm 4-1, a plano-convex lens 4-2, a movable plano-concave lens 4-3, a movable plano-concave lens 4-4, a cylindrical lens group 4-5 mounted on a motorized rotary displacement stage, a two-dimensional galvanometer system 4-6, a double cemented lens 4-7, a double cemented lens 4-8, a mirror 4-9, a reversible mirror 4-10, and a movable objective lens group 4-11.

[0029] As shown, Figure 1 The array ultrasound acquisition system assembly includes a ring-shaped ultrasound array system 5-1 and an acquisition system 5-2.

[0030] In particular, the system further includes a computer 6.

[0031] Specifically, the line light scanning-based photoacoustic mesoscopic imaging is realized in the following manner: the NIR pulsed laser emitted by the NIR nanosecond pulsed laser 1-1 is focused by the plano-convex lens 2-1 to the incident end face of the hexagonal homogenizing rod 2-2, and the focal point is located inside the cavity of the hexagonal homogenizing rod 2-2, and then collimated by the plano-convex lens 2-3 to obtain a circular near-flat light spot after the divergence angle is improved and shaped, and the corresponding light path is switched by the strip-in mirror 3-1 according to specific imaging requirements. The first path is a large-field deep-penetration depth light path, the laser reflected by the strip-in mirror 3-1 changes the spot size through the mirror 3-2 and the adjustable diaphragm 3-3, and the required scanning line light is obtained on the acoustic focal zone of the ring-shaped ultrasound array system 5-1 through the cooperative action of the cylindrical lens group 3-4 mounted on the motorized rotary displacement stage, the two-dimensional large-beam galvanometer system 3-5, and the f-theta lens 3-6. The second path is a small-field high-resolution light path, and the corresponding plano-concave lens is selected by adjusting the movable plano-concave lenses 4-3 and 4-4 according to the resolution requirement, the corresponding objective lens is switched by adjusting the movable objective lens group 4-11, and finally the reversible mirror 4-10 is opened. The laser passing through the cage structure of the strip-in mirror 3-1 changes the spot size through the adjustable diaphragm 4-1, the plano-convex lens 4-2, and the movable plano-concave lens (4-3 or 4-4), and the laser is introduced into the corresponding objective lens entrance pupil of the movable objective lens group 4-11 through the cooperative action of the cylindrical lens group 4-5 mounted on the motorized rotary displacement stage, the two-dimensional galvanometer system 4-6, and the 4-f system composed of the double cemented lens 4-7 and the double cemented lens 4-8, and is reflected twice by the mirror 4-9 and the reversible mirror 4-10, and the required scanning line light is obtained on the acoustic focal zone of the ring-shaped ultrasound array system 5-1. The photoacoustic signals excited by the scanned region are received by the ring-shaped ultrasound array system 5-1, acquired by the acquisition system 5-2, and stored in the computer 6.

[0032] Specifically, the scanning mechanism of the application is realized by the following steps: (1) The computer 6 sends instructions to control the column lens group (3-4 or 4-5) installed on the electric rotary displacement table to rotate to the first angle and enable fixation, turn on the NIR nanosecond pulsed laser 1-1 to emit NIR pulsed laser, and synchronize the two-axis large-beam galvanometer system 3-5 or two-dimensional galvanometer system 4-6 to enable to the first linear light scanning position. The first laser pulse forms a linear light on the imaging surface to excite the first photoacoustic time sequence signal, which is received by the annular ultrasonic array system 5-1 and collected by the acquisition system 5-2, and is immediately stored in the computer 6. Through the coordinated rotation of the two-axis large-beam galvanometer system 3-5 or two-dimensional galvanometer system 4-6, the linear light is scanned to the second linear light position, and the second laser pulse corresponds to excite the second photoacoustic time sequence signal, which is received by the annular ultrasonic array system 5-1 and collected by the acquisition system 5-2, and is immediately stored in the computer 6. When the linear light is scanned to the last linear light position, a matrix composed of all photoacoustic signals corresponding to the first linear light angle is obtained.

[0033] (2) Control the column lens group (3-4 or 4-5) installed on the electric rotary displacement table to rotate to the next angle and enable fixation through the control system 3-7, repeat step (1), and start full-field scanning at the next angle; (3) Repeat step (2) until the total rotation angle of the column lens group (3-4 or 4-5) installed on the electric rotary displacement table covers 180°, complete the data acquisition of the full linear light angle, and obtain the corresponding photoacoustic signal matrix in the computer 6.

[0034] The basic principle of the photoacoustic computed mesoscale imaging reconstruction method based on linear light scanning according to the application is as shown in Figure 2 The original sound pressure excited by a certain linear light angle can be represented by the following formula:

[0035] Wherein, is the initial sound pressure generated by the pulsed laser irradiation target object, is the linear light focusing direction, is the sound speed, is the two-dimensional spatial position of the annular array element, t is the flight time of the generated photoacoustic signal, and C is the thermodynamic constant parameter, is the photoacoustic signal sequence collected at the angle, which is directly related to the acoustic resolution and is determined by the bandwidth and center frequency of the annular ultrasonic array system 5-1 and the sampling rate of the acquisition system 5-2. When is small enough, ​The initial sound pressure is obtained by fidelity However, the real physical world cannot meet this condition, therefore, the present application proposes to reconstruct by the following formula:

[0036] The integral time window is determined based on the line light focusing width by performing threshold time domain integration on the photoacoustic signal of each line light scanning angle For each line light scanning angle, the acoustic resolution limit can be broken through by multi-angle data fusion, and isotropic high optical resolution computed imaging can be realized.

[0037] The photoacoustic computed mesoscopic imaging effect based on line light scanning of the present application is compared with the traditional photoacoustic imaging effect as shown in Figure 3 The imaging results of the complete scalp skull 12-week-old mouse brain vascular network of the photoacoustic computed mesoscopic imaging and the photoacoustic computed tomography imaging from left to right are shown, and both use 780nm laser to excite photoacoustic signal. It can be seen from the figure that the vascular network of the photoacoustic computed mesoscopic imaging result is more dense, complex and continuous, and the multi-stage vascular branch can be clearly seen, the vascular edge is more sharp, the detail contrast is higher, the vascular morphology is natural, the subtle change of the vascular diameter and the natural bending can be observed, the visualization of the mouse brain vascular network shows higher resolution and contrast, the vascular details can be better distinguished, which is beneficial to the later high-fidelity vascular structure quantitative analysis. The photoacoustic computed tomography imaging has excellent penetration depth, however, due to the acoustic resolution limit, only the main stem blood vessels and part of the branches can be clearly shown in the figure, the vascular boundary is not clear enough, the overall vascular signal-to-background ratio is low, which brings greater challenge to the quantitative structure analysis.

[0038] The specific implementation cases described in the present application are only examples of the main idea of the present application. Those skilled in the art to which the present application belongs can make various modifications or supplements to the described specific embodiments or replace them with similar ways, but will not deviate from the spirit of the present application or exceed the scope defined by the appended claims.

Claims

1. A photoacoustic computational mesoscopic imaging device based on line-optical scanning, characterized in that: Includes light source components, optical path modulation components, line light scanning components, array ultrasound acquisition system components, and a computer; The light source assembly includes an NIR nanosecond pulsed laser and a function generator. The NIR nanosecond pulsed laser is externally triggered and electrically connected to the function generator. The NIR pulsed laser emitted by the laser enters the line light scanning assembly after passing through the optical path modulation assembly. The function generator is used for synchronizing laser pulses, scanning control, and data acquisition. The optical path modulation assembly includes a lens group and a hexagonal light-uniforming rod, which are used to improve the divergence angle of the NIR pulsed laser and to shape and homogenize the light spot to obtain a circular near-flat-top light. The line beam scanning assembly includes an elliptical spot modulation assembly, a scanning system assembly, and a line beam modulation assembly. The elliptical spot modulation assembly includes a slotted mirror, a variable aperture, a plano-convex-plano-concave lens group, and a cylindrical lens group, used to generate an elliptical spot corresponding to the line beam with the required field of view resolution and imaging depth. The slotted mirror is used to switch different optical paths according to different imaging needs. The scanning system assembly includes an electrically driven rotary stage and a two-dimensional galvanometer system. The electrically driven rotary stage is used to mount the cylindrical lens group and obtain the required line beam angle through coaxial rotation. The two-dimensional galvanometer system is used to scan line beams at specific angles. Both are connected to the function generator of the light source assembly to ensure synchronous control. The line beam modulation assembly includes a 4-f cemented doublet lens assembly, an objective lens, a detachable objective lens switching device, and an f-theta lens, used to generate the line beam required for imaging. The focal plane of the objective lens is set to be coplanar with the focal plane of the f-theta lens. The array ultrasound acquisition system components include a line-focused low-frequency ultrasound ring array, a multi-channel high sampling rate data acquisition system, an elastic light- and sound-transmitting membrane, and a translational lifting platform. The acoustic focal zone of the ultrasonic ring array is coplanar with the optical focal zone of the f-theta lens of the linear light modulation component, thereby improving the ultrasonic acquisition sensitivity. The ultrasonic ring array is electrically connected to the data acquisition system, which integrates a signal amplifier and a data acquisition card for acquiring photoacoustic data. An elastic light- and sound-transparent membrane is installed at the bottom of the ultrasonic ring array to separate the imaging object from the pure water injected into the ring array for acoustic coupling. The translation and lifting platform is used to fix the imaging object and adjust the imaging surface to the acoustic and optical focal plane. The computer is used to control the scanning operation and data acquisition and storage of the photoacoustic computational mesoscopic imaging device.

2. The photoacoustic computational mesoscopic imaging device based on line optical scanning according to claim 1, characterized in that: The light source assembly and the optical path modulation assembly operate as follows: the NIR pulsed laser emitted by the NIR nanosecond pulsed laser is focused onto the incident end face of the hexagonal uniform light rod by a plano-convex lens, with the focal point located inside the cavity of the hexagonal uniform light rod. After being collimated by another plano-convex lens, a circular near-flat-top light spot with improved divergence angle and shaping is obtained and then led to the subsequent optical path.

3. The photoacoustic computational mesoscopic imaging device based on line optical scanning according to claim 1, characterized in that: The linear scanning component guides a circular near-flat-top beam into two optical paths via a strip-type reflector, based on the required field-of-view resolution and imaging depth. The two optical paths are designed for different field-of-view resolution requirements.

4. The photoacoustic computational mesoscopic imaging device based on line optical scanning according to claim 3, characterized in that: The first of the two optical paths is a large field-of-view, deep-penetration optical path. The variable aperture changes the spot size and optimizes the edge quality of the spot. The circular collimated spot is modulated into a short-axis focused elliptical spot by the cylindrical lens group, wherein the major axis length is consistent with the nominal effective entrance pupil of the f-theta lens and remains collimated, and the focal point in the short axis direction coincides with the entrance pupil of the f-theta lens. The light is reflected into the entrance pupil of the f-theta lens by the two-dimensional galvanometer system, and the desired line light is obtained on the optical focal plane of the f-theta lens. The cylindrical lens group is rotated along the optical axis by the electric rotary displacement stage to change the angle of the line light. The two mirrors of the two-dimensional galvanometer system rotate in concert to scan the line light on the two-dimensional focal plane along the focusing direction of the line light.

5. The photoacoustic computational mesoscopic imaging device based on line optical scanning according to claim 3, characterized in that: The second of the two optical paths is a small field-of-view, high-resolution optical path. The variable aperture first initially changes the spot size and optimizes the edge quality of the spot. Then, the plano-convex-plano-concave lens group changes the spot size over a wide range. The circular collimated spot is modulated into a collimated elliptical spot of a specific size by the cylindrical lens group. By switching the plano-concave lens, the major axis length is ensured to be consistent with the nominal effective entrance pupil of the corresponding objective lens. The two-dimensional galvanometer system and the 4-f cemented doublet lens combination reflect the light into the entrance pupil of the corresponding objective lens, obtaining the desired line light on the optical focal plane of the objective lens. The cylindrical lens group is rotated along the optical axis by the electric rotary displacement stage to change the angle of the line light. The two mirrors of the two-dimensional galvanometer system rotate in concert to scan the line light on the two-dimensional focal plane along the focusing direction of the line light.

6. The photoacoustic computational mesoscopic imaging device based on line optical scanning according to claim 1, characterized in that: The linear scanning component operates as follows: the motorized rotary stage and the two-dimensional galvanometer system work together. When the motorized rotary stage rotates to each fixed angle, the two-dimensional galvanometer system performs a full-field scan. The scanning direction is parallel to the linear beam focusing direction, and the scanning step size is determined by the width of the linear beam focusing direction, which must meet the dense sampling standard. The scanning range is the square circumscribed by the desired imaging circular field of view. A suitable number of angles K is selected according to the imaging field of view and the width of the linear beam focusing direction. The number of array elements of the ring array is N, and the number of scanned linear beams at each angle is the scanning range width divided by the scanning step size, denoted as M.

7. The photoacoustic computational mesoscopic imaging device based on line optical scanning according to claim 6, characterized in that: The array ultrasound acquisition system components and computer operate as follows: the photoacoustic signal excited by each line beam is converted into a one-dimensional time-intensity sequence signal array by the acquisition system. The array length is denoted as A, and A is set by the acquisition card acquisition frequency and the laser pulse repetition frequency. The acquisition card simultaneously acquires all array data N×A. The M×N×A data acquired at each line beam scanning angle is stored once on the computer, and the buffer is cleared before the next angle data acquisition is performed. The final photoacoustic data collected is stored and processed by a computer, and the data storage format is a four-dimensional matrix of K×M×N×A.

8. A photoacoustic computational mesoscopic imaging method based on line optical scanning, characterized in that, The non-destructive mesoscopic imaging of the object under test is obtained using the photoacoustic computational mesoscopic imaging device based on line optical scanning as described in any one of claims 1-7, and the steps are as follows: Step S1: Fix the imaging target on the translation and lifting platform, and slowly move the imaging surface to the focal plane where the sound and light coincide, so that the elastic light-transmitting and sound-transmitting film is in close contact with the imaging object. During the live imaging process, the subject to be tested is continuously anesthetized using an air anesthesia machine. Step S2: Add pure water to the ultrasonic ring array to fill the entire array cavity; Step S3: Based on the required field resolution and imaging depth, select the corresponding optical path using a plug-in reflector, preset the number of line beam angles K, calculate the number of single-angle scan lines M by the line beam scanning range and scanning step size, the line beam scanning direction is the line beam focusing direction, and plan the enable voltage of each axis of the two-dimensional galvanometer system corresponding to the specific position parameters of M line beams under each line beam angle. Step S4: The computer controls the electric rotary stage to rotate to the set first angle and fix it, triggering the NIR nanosecond pulse laser to emit NIR pulse laser light. Simultaneously, the two axes of the two-dimensional galvanometer system are enabled to the first line beam position. The line beam is obtained on the imaging surface after passing through the optical path modulation component and the line beam scanning component. The first laser pulse correspondingly excites the first photoacoustic timing signal, which is acquired by the array ultrasonic acquisition system component, and a 1×1×N×A matrix is ​​stored in the computer in real time. Through the coordinated rotation of the two axes of the two-dimensional galvanometer system, the line beam is scanned to the second line beam position. The second laser pulse correspondingly excites the second photoacoustic timing signal, which is acquired by the array ultrasonic acquisition system component, and similarly, a 1×1×N×A matrix is ​​stored in the computer in real time. When the line beam scans to the Mth line beam position, a 1×M×N×A matrix composed of all photoacoustic signals corresponding to the first line beam angle is obtained. Step S5: By controlling the electric rotary displacement stage to rotate to the set next angle and enabling it to be fixed, the NIR nanosecond pulse laser is triggered. Step S4 is repeated to start the full field-of-view scan of the next angle. Step S6: Repeat step S5 until the total rotation angle of the electric rotary displacement stage covers 180˚, complete the data acquisition of the optical angle of the entire line, and obtain the corresponding K×M×N×A photoacoustic signal matrix in the computer. Step S7: Based on the obtained photoacoustic signal matrix, the test object is reconstructed to obtain non-destructive mesoscopic brain imaging results.

9. The photoacoustic computational mesoscopic imaging method based on line optical scanning according to claim 8, characterized in that, In step S7, reconstruction is performed using the following formula: in, It is the initial sound pressure generated by pulsed laser radiation on the target object. It is the direction of line light focusing. It's the speed of sound. t represents the two-dimensional spatial position of the elements in the ring array, t represents the flight time of the generated photoacoustic signal, and C is a thermodynamic constant parameter. for The sequence of photoacoustic signals acquired at a specific angle. The integration time window is determined by the width of the line beam focusing direction and the sampling rate of the acquisition system.

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