Photoacoustic pumping imaging system based on pulse laser phase energy correction

Abstract

The invention provides a photoacoustic pumping imaging system based on pulse laser phase energy correction. The opto-acoustic pumping imaging system based on pulse laser phase energy correction comprises a 128-channel array ultrasonic acquisition system, two OPO tunable lasers and a digital delay pulse generator which form the opto-acoustic pumping imaging system, a 128 array element linear ultrasonic transducer and a 2 * 2 multimode fiber bundle; and a pulse laser phase energy correction system which needs to monitor and correct the phase of the laser pulse. The opto-acoustic pumping imaging system based on pulse laser phase energy correction provided by the invention realizes accurate phase correction and energy normalization based on precise synchronization of two acquisition systems, so that the system can significantly reduce the fluctuation of TTD data, improve the stability and reliability of results, improve the acquisition speed and signal-to-noise ratio of the system, and improve the imaging quality of the system. The detection limit is reduced.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedical imaging, and in particular relates to a photoacoustic pumping imaging system based on pulse laser phase energy correction. Background Art

[0002] Traditional medical imaging diagnosis relies on changes in macroscopic anatomical structures or physiological functions, while molecular imaging technology can capture microscopic changes at the cellular and molecular levels in the early stages of the disease, thus having breakthrough advantages in early diagnosis, precise classification and treatment monitoring. However, the current mainstream molecular imaging technologies (i.e., radionuclide methods such as PET and SPECT) have problems such as high cost, low inherent spatial resolution, and risk of radioactive exposure. Although emerging nuclear magnetic molecular imaging technologies such as chemical exchange saturation transfer and magnetic resonance spectroscopy can achieve radiation-free, high-resolution molecular imaging, their excitation efficiency is limited by the difference in the magnitude of the nuclear Zeeman energy level difference and thermal energy (ΔE≤kBT), resulting in significant limitations in detection sensitivity, spatial resolution (larger voxels are required to improve the signal-to-noise ratio), and imaging speed. Hyperpolarized magnetic resonance technology works by enhancing the nuclear spin polarization (increasing the polarization by about times) overcomes the inherent defect of low excitation efficiency of magnetic resonance, but the lifetime of the hyperpolarized spin state is very short (usually < 1 minute), and it is currently only applicable to special scenarios such as lung gas imaging. In contrast, photoacoustic pump imaging not only inherits the advantages of traditional optical molecular imaging technology such as diverse molecular response mechanisms, good specificity, high excitation efficiency, low cost, and good portability, but also effectively overcomes the influence of strong optical scattering in tissues, realizing high-resolution molecular imaging in deep tissues; Traditional photoacoustic imaging technology is affected by strong background absorption such as tissue blood, making it difficult to obtain the precise distribution of photosensitizers and unable to image oxygen partial pressure.

[0003] Therefore, it is necessary to provide a new photoacoustic pumping imaging system based on pulsed laser phase energy correction to solve the above technical problems. Summary of the Invention

[0004] The technical problem solved by the present invention is to provide a photoacoustic pumping imaging system based on pulsed laser phase energy correction, which realizes accurate phase correction and energy normalization by combining the precise synchronization of two acquisition systems. The system can significantly reduce the volatility of TTD data, improve the stability and reliability of the results, increase the acquisition speed and signal-to-noise ratio of the system, and reduce the detection limit.

[0005] To solve the above technical problems, the present invention provides a photoacoustic pumping imaging system based on pulsed laser phase energy correction, which includes: a 128-channel array ultrasound acquisition system, two OPO tunable lasers, a digital delayed pulse generator, a 128-element linear ultrasound transducer, a 2×2 multimode fiber bundle, and a pulsed laser phase energy correction system for monitoring and correcting the phase of the laser pulse. When the photoacoustic pump imaging system starts the acquisition task, the array ultrasound acquisition system will send out a 20 Hz acquisition clock 9, which will be received by the digital delay pulse generator, thereby outputting a control clock 6 according to a pre-written program; The clock includes five trigger clock signals, namely the pump laser flash signal, the pump laser Q-Switch signal, the detection laser flash signal, the detection laser Q-Switch signal and the clock signal of the high-speed acquisition system, wherein the delay required for the flash signals of the two lasers and the Q-Switch to achieve the maximum energy of the laser is 216 μs, the delay of the pump laser flash signal and the detection laser flash signal is 0.3 μs, and the clock signal of the high-speed acquisition system is consistent with the acquisition clock 9; The clock signal of the laser can control the two tunable OPO lasers to be excited in a predetermined time sequence. The repetitive frequency of the laser is 20 Hz. The pump light OPO laser will emit a 665 nm wavelength laser 1 to excite the target molecule methylene blue (MB) in the ground state in the biological tissue. After 0.3 microseconds, the detection light OPO laser will emit an 820 nm wavelength laser 2 to detect the target molecule in the excited state. In this process, the pulsed lasers emitted by the two lasers will be projected to the target object through a 2×2 multimode fiber bundle 4. These lasers will excite photoacoustic signals 5 in the target tissue. These signals are received by the array ultrasonic transducer and converted into electrical signals 10, and finally received by the array ultrasonic acquisition system.

[0006] As a further solution of the present invention, the center frequency of the 128-element linear ultrasonic transducer L11-5V is 8 MHz. In the photoacoustic pump imaging, the pump light excites the photosensitizer molecules to the singlet state, which enters the triplet state through intersystem crossing. The photoacoustic signal is then generated by the detection light-induced non-radiative transition. Such photosensitizer molecules with long-lived triplet states can be used as a repeatedly activated optical switch photoacoustic probe. The absorption spectrum can be changed by the pump light during its triplet state lifetime. However, biological background tissue does not have this effect because the excited state lifetime is shorter than the light pulse. Therefore, by differentially analyzing the photoacoustic signals generated by the detection light with and without the pump light, highly specific molecular detection can be achieved.

[0007] As a further solution of the present invention, fast and accurate photoacoustic pump imaging can be achieved by monitoring the laser pulse. For example, assuming that the concentration of the photosensitizer molecules is 0, the amplitude and phase are and The amplitude of the differential signal caused by the fluctuation of the background photoacoustic signal can be expressed as formula (2): , In the formula: represents the fluctuation of the photoacoustic signal amplitude, represents the fluctuation of its phase, is the center frequency of the sound wave, Indicates the delay time.

[0008] As a further solution of the present invention, the pulsed laser phase energy correction system consists of a multi-channel high-speed acquisition card, a JSR pulse generator / receiver and a high-speed photodiode. The multi-channel high-speed acquisition card is M4i.221X, 4 channels, 8 bits, and a sampling rate of 1.25 GS / s. The wavelength response range of the high-speed photodiode is 300nm-1100nm, the cutoff frequency is greater than 1GHz, and the rising edge is less than 1ns.

[0009] As a further solution of the present invention, when the two lasers emit lasers, part of the laser energy is reflected into the photosensitive part of the high-speed photodiode through two partial reflectors 3. The high-speed photodiode will collect this photoelectric signal 7, which is finally collected by the high-speed acquisition card. The high-speed acquisition card will simultaneously collect the ultrasonic signal 8 generated by a certain array element of the linear ultrasonic transducer (the system collects the 64th array element). The high-frequency ultrasonic signal will be phase-compensated with the low-frequency ultrasonic signal to eliminate the clock jitter. In the case of the same clock error, the photoelectric signal collected by the high-speed acquisition card can be obtained. 、 、 The relative phase jitter of the pulsed laser between the minutes and the energy jitter corresponding to each signal.

[0010] As a further solution of the present invention, selecting a reasonable combination of pump and probe light wavelengths can further improve the specificity of photoacoustic pump imaging for target molecules. For example, the TTD signal of the photosensitizer can be expressed as formula (1): , In the formula: is the TTD signal obtained by subtracting the background. is the photoacoustic signal when the pump and probe light are excited simultaneously, is the photoacoustic signal generated by pump light excitation only, is the photoacoustic signal generated by the detection light excitation only, and t is the delay time of the detection laser relative to the pump laser.

[0011] As a further solution of the present invention, the phase is determined by the synchronization error between the acquisition system and the laser light. For example, the clock error between the high-speed acquisition card and the photoacoustic signal acquisition system is obtained by acquiring the ultrasonic signal through a high-speed acquisition card, and each light pulse signal is obtained through a high-speed photodiode. Therefore, by calculating the cross-correlation of each light pulse, the offset information of the light pulse on the time axis - the phase - can be obtained.

[0012] As a further solution of the present invention, the amplitude of the initial sound pressure of the photoacoustic signal is It is proportional to the energy density F of the pulsed laser at a local position. Therefore, the integral result of the optical pulse waveform represents the optical energy density at each time. By adjusting the signal amplitude accordingly through the proportional coefficient corresponding to the energy, the photoacoustic signal amplitude can be corrected - energy normalization.

[0013] As a further solution of the present invention, the amplitude of the initial sound pressure of the photoacoustic signal is The relationship with the energy density F of the pulsed laser at a local position can be expressed as: , in, is the Grüneisen coefficient, which characterizes the efficiency of the medium in converting the absorbed thermal energy into mechanical pressure (sound waves). is the optical absorption coefficient, which indicates the absorption capacity of the medium to the laser of a specific wavelength; It is wavelength-dependent and determines the proportion of light energy absorbed per unit length. F is the local light energy density, which refers to the laser pulse energy that reaches and deposits at a specific point or small volume element. Therefore, in a specific medium ( , Fixed) and specific irradiation conditions, the initial sound pressure amplitude Proportional to the local light energy density F; There is nanosecond-level time jitter in the actual synchronization process between the photoacoustic signal acquisition system and the pulsed laser light output. Therefore, when the sound wave propagates from the generation point to the detector, different time offsets Δt are generated. Considering the frequency domain, if the photoacoustic signal is Fourier transformed, each frequency component will have a phase, and the relationship between this phase and time delay is: , Where is the initial phase, which is determined by the nature of the source and can usually be assumed to be 0, and f is the frequency. Therefore, the phase slope is proportional to the time offset, so the photoacoustic signal amplitude is It determines the amplitude of the waveform, while the time offset determines the position of the waveform on the time axis, that is, the phase.

[0014] As a further solution of the present invention, the phase jitter of the photoacoustic signal acquisition system is calculated by Its own phase fluctuations and 、 The total phase fluctuation of the three is the sum of the clock fluctuation and phase jitter of the signal. When reconstructing these signals, the total phase fluctuation will be compensated by the reconstruction delay, and the energy can be the maximum value of the corresponding optical pulse or the integral of the waveform. When taking the difference of the three signals, the corresponding adjustment is made through the energy proportional coefficient.

[0015] Compared with related technologies, the photoacoustic pumping imaging system based on pulsed laser phase energy correction provided by the present invention has the following beneficial effects: 1. The present invention monitors laser pulses through a multi-channel GHz high-frequency acquisition system, overcoming the low sampling frequency drawback of conventional array ultrasound acquisition systems. Combined with the precise synchronization of two acquisition systems, accurate phase correction and energy normalization are achieved. Therefore, the system can significantly reduce the volatility of TTD data, improve the stability and reliability of the results, increase the system's acquisition speed and signal-to-noise ratio, and lower the detection limit. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] To facilitate understanding by those skilled in the art, the present invention is further described below with reference to the accompanying drawings.

[0017] Figure 1 Schematic diagram of the photoacoustic pumping system based on pulsed laser phase energy correction of the present invention; Figure 2 Schematic diagram of TTD results of the phantom test tube before and after pulse laser phase energy correction under different pump-probe delays and different solutions of the present invention; Figure 3 Schematic diagram of the phantom test tube results of the present invention with a 10 mg / mL bovine hemoglobin solution mixed with MB at different concentration gradients. DETAILED DESCRIPTION

[0018] The photoacoustic pumping imaging system based on pulsed laser phase energy correction provided by the present invention includes: a 128-channel array ultrasound acquisition system, two OPO tunable lasers, a digital delayed pulse generator, a 128-element linear ultrasound transducer, a 2×2 multimode fiber bundle, and a pulsed laser phase energy correction system for monitoring and correcting the phase of the laser pulse. When the photoacoustic pump imaging system starts the acquisition task, the array ultrasound acquisition system will send out a 20 Hz acquisition clock 9, which will be received by the digital delay pulse generator, thereby outputting a control clock 6 according to a pre-written program; The clock includes five trigger clock signals, namely the pump laser flash signal, the pump laser Q-Switch signal, the detection laser flash signal, the detection laser Q-Switch signal and the clock signal of the high-speed acquisition system, wherein the delay required for the flash signals of the two lasers and the Q-Switch to achieve the maximum energy of the laser is 216 μs, the delay of the pump laser flash signal and the detection laser flash signal is 0.3 μs, and the clock signal of the high-speed acquisition system is consistent with the acquisition clock 9; The clock signal of the laser can control the two tunable OPO lasers to be excited in a predetermined time sequence. The repetitive frequency of the laser is 20 Hz. The pump light OPO laser will emit a 665 nm wavelength laser 1 to excite the target molecule methylene blue (MB) in the ground state in the biological tissue. After 0.3 microseconds, the detection light OPO laser will emit an 820 nm wavelength laser 2 to detect the target molecule in the excited state. In this process, the pulsed lasers emitted by the two lasers will be projected to the target object through a 2×2 multimode fiber bundle 4. These lasers will excite photoacoustic signals 5 in the target tissue. These signals are received by the array ultrasonic transducer and converted into electrical signals 10, and finally received by the array ultrasonic acquisition system.

[0019] The center frequency of the 128-element linear ultrasonic transducer L11-5V is 8 MHz. In the photoacoustic pump imaging, the pump light excites the photosensitizer molecules to the singlet state, which then enters the triplet state through intersystem crossing. The detection light then induces non-radiative transitions to generate photoacoustic signals. These photosensitizer molecules with long-lived triplet states can be used as repeatedly activated optical switchable photoacoustic probes. Their absorption spectrum can be altered by pump light during their triplet state lifetime. However, biological background tissue does not experience this effect because the excited state lifetime is shorter than the light pulse. Therefore, by differentially analyzing the photoacoustic signals generated by the detection light with and without the pump light, highly specific molecular detection can be achieved.

[0020] By monitoring the laser pulse, fast and accurate photoacoustic pump imaging can be achieved. For example, assuming that the concentration of the photosensitizer molecules is 0, the amplitude and phase are A and The amplitude of the differential signal caused by the fluctuation of the background photoacoustic signal can be expressed as formula (2): , In the formula: represents the fluctuation of the photoacoustic signal amplitude, represents the fluctuation of its phase, f is the center frequency of the sound wave, Indicates the delay time.

[0021] The pulsed laser phase energy correction system consists of a multi-channel high-speed acquisition card, a JSR pulse generator / receiver, and a high-speed photodiode. The multi-channel high-speed acquisition card is an M4i.221X, 4-channel, 8-bit, 1.25 GS / s sampling rate. The high-speed photodiode has a wavelength response range of 300nm-1100nm, a cutoff frequency greater than 1GHz, and a rising edge of less than 1ns.

[0022] When the two lasers emit lasers, part of the laser energy is reflected into the photosensitive part of the high-speed photodiode through two partial reflective mirrors 3. The high-speed photodiode will collect this photoelectric signal 7, which is finally collected by the high-speed acquisition card. The high-speed acquisition card will simultaneously collect the ultrasonic signal 8 generated by a certain array element of the linear ultrasonic transducer (the system collects the 64th array element). The high-frequency ultrasonic signal will be phase-compensated with the low-frequency ultrasonic signal to eliminate the clock jitter. In the case of the same clock error, the photoelectric signal collected by the high-speed acquisition card can be obtained. 、 、 The relative phase jitter of the pulsed laser between the minutes and the energy jitter corresponding to each signal.

[0023] Choosing a reasonable combination of pump and probe wavelengths can further improve the specificity of photoacoustic pump imaging for target molecules. For example, the TTD signal of a photosensitizer can be expressed as formula (1): , In the formula: is the TTD signal obtained by subtracting the background. is the photoacoustic signal when the pump and probe light are excited simultaneously, is the photoacoustic signal generated by pump light excitation only, is the photoacoustic signal generated by the detection light excitation only, and t is the delay time of the detection laser relative to the pump laser.

[0024] The phase is determined by the synchronization error between the acquisition system and the laser light. For example, the clock error between the high-speed acquisition card and the photoacoustic signal acquisition system is obtained by acquiring the ultrasonic signal through a high-speed acquisition card, and each light pulse signal is obtained through a high-speed photodiode. Therefore, by calculating the cross-correlation of each light pulse, the offset information of the light pulse on the time axis - the phase - can be obtained.

[0025] The amplitude of the initial sound pressure of the photoacoustic signal It is proportional to the energy density F of the pulsed laser at a local position. Therefore, the integral result of the optical pulse waveform represents the optical energy density at each time. By adjusting the signal amplitude accordingly through the proportional coefficient corresponding to the energy, the photoacoustic signal amplitude can be corrected - energy normalization.

[0026] The amplitude of the initial sound pressure of the photoacoustic signal The relationship with the energy density F of the pulsed laser at a local position can be expressed as: , in, is the Grüneisen coefficient, which characterizes the efficiency of the medium in converting the absorbed thermal energy into mechanical pressure (sound waves). is the optical absorption coefficient, which indicates the absorption capacity of the medium to the laser of a specific wavelength; It is wavelength-dependent and determines the proportion of light energy absorbed per unit length. F is the local light energy density, which refers to the laser pulse energy that reaches and deposits at a specific point or small volume element. Therefore, in a specific medium ( , Fixed) and specific irradiation conditions, the initial sound pressure amplitude Proportional to the local light energy density F; There is nanosecond-level time jitter in the actual synchronization process between the photoacoustic signal acquisition system and the pulsed laser light output. Therefore, when the sound wave propagates from the generation point to the detector, different time offsets Δt are generated. Considering the frequency domain, if the photoacoustic signal is Fourier transformed, each frequency component will have a phase, and the relationship between this phase and time delay is: , in, is the initial phase, which is determined by the nature of the source and can usually be assumed to be 0, and f is the frequency. Therefore, the phase slope is proportional to the time offset, so the photoacoustic signal amplitude is It determines the amplitude of the waveform, while the time offset determines the position of the waveform on the time axis, that is, the phase.

[0027] The phase jitter of the photoacoustic signal acquisition system is calculated by Its own phase fluctuations and 、 The total phase fluctuation of the three is the sum of the clock fluctuation and phase jitter of the signal. When reconstructing these signals, the total phase fluctuation will be compensated by the reconstruction delay, and the energy can be the maximum value of the corresponding optical pulse or the integral of the waveform. When taking the difference of the three signals, the corresponding adjustment is made through the energy proportional coefficient.

[0028] The accompanying drawings are for illustrative purposes only and are not to be construed as limiting this patent; The technical solution of the present invention is further described below with reference to the accompanying drawings and embodiments.

[0029] Example 1

[0030] This embodiment provides a photoacoustic pumping imaging system based on pulsed laser phase energy correction, including: system hardware configuration and signal acquisition; 1. Hardware construction: according to Figure 1 Connect various components to ensure that the 128-channel array ultrasound acquisition system, two OPO tunable lasers, digital delayed pulse generator, 128-element linear ultrasound transducer and 2×2 multimode fiber bundle are correctly connected. The multi-channel high-speed acquisition card, JSR pulse generator / receiver and high-speed photodiode of the pulse laser phase energy correction part are installed and debugged.

[0031] 2. Signal acquisition: Set the pump light wavelength to 665nm, the probe light wavelength to 820nm, and the laser repetition frequency to 20Hz. For a 200μmol / L pure MB solution, a 10mg / mL bovine hemoglobin solution, and a 10mg / mL bovine hemoglobin solution mixed with 200μmol / L MB, set the pump light and probe light delays to 0.2μs, 0.3μs, 0.5μs, 2μs, 4μs, 6μs, 8μs, and 16μs, respectively. Start the system to collect photoacoustic signals. Figure 2 In the figure, (a) is the TTD of 200 μmol / L MB at different pump-probe delays; (b) is the TTD of 10 mg / mL bovine hemoglobin solution at different pump-probe delays; (c) is the TTD of 10 mg / mL bovine hemoglobin solution mixed with 200 μmol / L MB at different pump-probe delays; (d) is the STD of 200 μmol / L MB at different pump-probe delays; (e) is the STD of 10 mg / mL bovine hemoglobin solution at different pump-probe delays; (f) is the STD of 10 mg / mL bovine hemoglobin solution mixed with 200 μmol / L MB at different pump-probe delays.

[0032] Figure 3 In the figure, (a) is the TTD of a phantom test tube containing a 10 mg / mL bovine hemoglobin solution mixed with different concentration gradients of MB; (b) is the STD of a phantom test tube containing a 10 mg / mL bovine hemoglobin solution mixed with different concentration gradients of MB.

[0033] Example 2

[0034] This embodiment provides a photoacoustic pumping imaging system based on pulsed laser phase energy correction, including: data processing and correction; 1. Phase Correction: A high-speed acquisition card is used to collect the laser pulse signal output by the high-speed photodiode and the ultrasonic signal from the 64th element of the linear ultrasonic transducer. The cross-correlation between the two is calculated to obtain the offset information (phase) of the light pulse on the time axis. Based on the relationship between phase and time delay, the phase of the photoacoustic signal is compensated.

[0035] 2. Energy normalization: The integral result of the optical pulse waveform represents the optical energy density at each time. Based on the proportional relationship between the photoacoustic signal amplitude and energy density, the signal amplitude is adjusted to achieve energy normalization.

[0036] Example 3

[0037] This embodiment provides a photoacoustic pumping imaging system based on pulse laser phase energy correction, including: experimental results analysis; 1.TTD signal stability: Figure 2 As shown in the figure, the change in the TTD signal value after energy and phase calibration conforms to the attenuation trend of methylene blue with time delay. The change trend of the TTD signal of the bovine hemoglobin solution mixed with MB is consistent with that of the pure MB solution, indicating that the system can stably acquire the target signal under strong background interference. The STD of the bovine hemoglobin solution decreased by about 68%, the STD of the mixed solution decreased by 60%, and the STD of the MB solution decreased by 34%, indicating that the correction system significantly reduced data volatility. 2. Detection limit and imaging speed: Figure 3 As shown in the figure, the amplitude of the TTD signal after correction is linearly related to the MB concentration within a certain range. There is a significant difference between the 10 μmol / LMB solution and the 0 μmol / L solution, while there is no significant difference before correction. The detection limit is improved. At the same time, the STD is greatly reduced. Under the same number of averaging times, the acquisition speed can be increased by about 8 times, which improves the overall performance of the system.

[0038] The above description is only a preferred specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes based on the technical solutions and inventive concepts of the present invention within the technical scope disclosed by the present invention, and they should be covered by the scope of protection of the present invention.

Claims

1. A photoacoustic pumping imaging system based on pulsed laser phase energy correction, characterized in that: include: The photoacoustic pumping imaging system consists of a 128-channel array ultrasound acquisition system, two OPO tunable lasers, a digital delayed pulse generator, a 128-element linear ultrasound transducer, a 2×2 multimode fiber bundle, and a pulsed laser phase energy correction system for monitoring and correcting the laser pulse phase. When the photoacoustic pump imaging system starts the acquisition task, the array ultrasound acquisition system will send out a 20 Hz acquisition clock 9, which will be received by the digital delay pulse generator, thereby outputting a control clock 6 according to a pre-written program; The clock includes five trigger clock signals, namely the pump laser flash signal, the pump laser Q-Switch signal, the detection laser flash signal, the detection laser Q-Switch signal and the clock signal of the high-speed acquisition system, wherein the delay required for the flash signals of the two lasers and the Q-Switch to achieve the maximum energy of the laser is 216 μs, the delay of the pump laser flash signal and the detection laser flash signal is 0.3 μs, and the clock signal of the high-speed acquisition system is consistent with the acquisition clock 9; The clock signal of the laser can control the two tunable OPO lasers to be excited in a predetermined time sequence. The repetitive frequency of the laser is 20 Hz. The pump light OPO laser will emit a 665 nm wavelength laser 1 to excite the target molecule methylene blue (MB) in the ground state in the biological tissue. After 0.3 microseconds, the detection light OPO laser will emit an 820 nm wavelength laser 2 to detect the target molecule in the excited state. In this process, the pulsed lasers emitted by the two lasers will be projected to the target object through a 2×2 multimode fiber bundle 4. These lasers will excite photoacoustic signals 5 in the target tissue. These signals are received by the array ultrasonic transducer and converted into electrical signals 10, and finally received by the array ultrasonic acquisition system.

2. The photoacoustic pumping imaging system based on pulsed laser phase energy correction according to claim 1, characterized in that: The center frequency of the 128-element linear ultrasonic transducer L11-5V is 8 MHz. In the photoacoustic pump imaging, the pump light excites the photosensitizer molecules to the singlet state, which then enters the triplet state through intersystem crossing. The detection light then induces non-radiative transitions to generate photoacoustic signals. These photosensitizer molecules with long-lived triplet states can be used as repeatedly activated optical switchable photoacoustic probes. Their absorption spectrum can be altered by pump light during their triplet state lifetime. However, biological background tissue does not experience this effect because the excited state lifetime is shorter than the light pulse. Therefore, by differentially analyzing the photoacoustic signals generated by the detection light with and without the pump light, highly specific molecular detection can be achieved.

3. The photoacoustic pumping imaging system based on pulsed laser phase energy correction according to claim 1, characterized in that: By monitoring the laser pulse, fast and accurate photoacoustic pump imaging can be achieved. For example, assuming that the concentration of the photosensitizer molecules is 0, the amplitude and phase are and The amplitude of the differential signal caused by the fluctuation of the background photoacoustic signal can be expressed as formula (2): ， In the formula: represents the fluctuation of the photoacoustic signal amplitude, represents the fluctuation of its phase, is the center frequency of the sound wave, Indicates the delay time.

4. The photoacoustic pumping imaging system based on pulsed laser phase energy correction according to claim 1, characterized in that: The pulsed laser phase energy correction system consists of a multi-channel high-speed acquisition card, a JSR pulse generator / receiver, and a high-speed photodiode. The multi-channel high-speed acquisition card is an M4i.221X, 4-channel, 8-bit, 1.25 GS / s sampling rate. The high-speed photodiode has a wavelength response range of 300nm-1100nm, a cutoff frequency greater than 1GHz, and a rising edge of less than 1ns.

5. The photoacoustic pumping imaging system based on pulsed laser phase energy correction according to claim 4, characterized in that: When the two lasers emit lasers, part of the laser energy is reflected into the photosensitive part of the high-speed photodiode through two partial reflective mirrors 3. The high-speed photodiode will collect this photoelectric signal 7, which is finally collected by the high-speed acquisition card. The high-speed acquisition card will simultaneously collect the ultrasonic signal 8 generated by a certain array element of the linear ultrasonic transducer (the system collects the 64th array element). The high-frequency ultrasonic signal will be phase-compensated with the low-frequency ultrasonic signal to eliminate the clock jitter. In the case of the same clock error, the photoelectric signal collected by the high-speed acquisition card can be obtained. 、 、 The relative phase jitter of the pulsed laser between the minutes and the energy jitter corresponding to each signal.

6. The photoacoustic pumping imaging system based on pulsed laser phase energy correction according to claim 5, characterized in that: Choosing a reasonable combination of pump and probe wavelengths can further improve the specificity of photoacoustic pump imaging for target molecules. For example, the TTD signal of a photosensitizer can be expressed as formula (1): ， In the formula: is the TTD signal obtained by subtracting the background. is the photoacoustic signal when the pump and probe light are excited simultaneously, is the photoacoustic signal generated by pump light excitation only, is the photoacoustic signal generated by the detection light excitation only, and t is the delay time of the detection laser relative to the pump laser.

7. The photoacoustic pumping imaging system based on pulsed laser phase energy correction according to claim 5, characterized in that: The phase is determined by the synchronization error between the acquisition system and the laser light. For example, the clock error between the high-speed acquisition card and the photoacoustic signal acquisition system is obtained by acquiring the ultrasonic signal through a high-speed acquisition card, and each light pulse signal is obtained through a high-speed photodiode. Therefore, by calculating the cross-correlation of each light pulse, the offset information of the light pulse on the time axis - the phase - can be obtained.

8. The photoacoustic pumping imaging system based on pulsed laser phase energy correction according to claim 7, characterized in that: The amplitude of the initial sound pressure of the photoacoustic signal It is proportional to the energy density F of the pulsed laser at a local position. Therefore, the integral result of the optical pulse waveform represents the optical energy density at each time. By adjusting the signal amplitude accordingly through the proportional coefficient corresponding to the energy, the photoacoustic signal amplitude can be corrected - energy normalization.

9. The photoacoustic pumping imaging system based on pulsed laser phase energy correction according to claim 8, characterized in that: The amplitude of the initial sound pressure of the photoacoustic signal The relationship with the energy density F of the pulsed laser at a local position can be expressed as: ， in, is the Grüneisen coefficient, which characterizes the efficiency of the medium in converting the absorbed thermal energy into mechanical pressure (sound waves). is the optical absorption coefficient, which indicates the absorption capacity of the medium to the laser of a specific wavelength; It is wavelength-dependent and determines the proportion of light energy absorbed per unit length. F is the local light energy density, which refers to the laser pulse energy that reaches and deposits at a specific point or small volume element. Therefore, in a specific medium ( , Fixed) and specific irradiation conditions, the initial sound pressure amplitude Proportional to the local light energy density F; There is nanosecond-level time jitter in the actual synchronization process between the photoacoustic signal acquisition system and the pulsed laser light output. Therefore, when the sound wave propagates from the generation point to the detector, different time offsets Δt are generated. Considering the frequency domain, if the photoacoustic signal is Fourier transformed, each frequency component will have a phase, and the relationship between this phase and time delay is: ， in, is the initial phase, which is determined by the nature of the source and can usually be assumed to be 0, and f is the frequency. Therefore, the phase slope is proportional to the time offset, so the photoacoustic signal amplitude is It determines the amplitude of the waveform, while the time offset determines the position of the waveform on the time axis, that is, the phase.

10. The photoacoustic pumping imaging system based on pulsed laser phase energy correction according to claim 9, characterized in that: The phase jitter of the photoacoustic signal acquisition system is calculated by Its own phase fluctuations and 、 The total phase fluctuation of the three is the sum of the clock fluctuation and phase jitter of the signal. When reconstructing these signals, the total phase fluctuation will be compensated by the reconstruction delay, and the energy can be the maximum value of the corresponding optical pulse or the integral of the waveform. When taking the difference of the three signals, the corresponding adjustment is made through the energy proportional coefficient.

Images