Multimodal imaging system based on radio-frequency programmable ghz femtosecond pulse train

Abstract

A multimodal imaging system based on a radio-frequency programmable GHz femtosecond pulse train. The system comprises: a femtosecond pulse laser light source (101), a pulse splitting module (102), a pulse amplification module (103), a pulse compression module (104), an imaging module (105), an optical signal collection component (106), an ultrasonic signal collection component (107) and a data processing component (108). Multiphoton imaging and photoacoustic imaging are performed simultaneously by means of the femtosecond pulse laser light source (101), and thus multi-dimensional real-time observation is implemented, and system integration is realized with a low cost.

Description

A multimodal imaging system based on radio frequency programmable GHz femtosecond pulse trains Technical Field

[0001] This invention relates to the fields of multimodal biomedical imaging and femtosecond laser technology, and particularly to a multimodal imaging system based on radio frequency programmable GHz femtosecond pulse trains. Background Technology

[0002] Multiphoton imaging technology, with its advantages of low invasiveness, strong penetration, high spatial resolution, and high selectivity, has become a powerful tool in biomedical research, playing a significant role in the study of deep brain tissue structure and physiological function, neurological diseases, and cancer pathology. Currently, two-photon excitation fluorescence microscopy is the most widely used multiphoton imaging technique. In recent years, three-photon excitation fluorescence microscopy has also been developing rapidly, showing great potential for application in the biomedical field.

[0003] Photoacoustic imaging, as an emerging biomedical imaging method, uses pulsed light to excite ultrasound signals. It has advantages such as being non-invasive, having high penetration depth, and high image contrast. It is an important tool for research on cardiovascular and cerebrovascular diseases, drug metabolism, gene expression, and immunity. Its broad application prospects will bring about a revolution in the field of clinical medical imaging in the future.

[0004] Because only certain biological tissues can effectively emit fluorescence, multiphoton imaging provides limited information without dye labeling. Photoacoustic imaging, on the other hand, does not require labeling. Therefore, if multiphoton and photoacoustic imaging can be performed simultaneously, more comprehensive information can be acquired, including fluorescently labeled biological tissue structures based on multiphoton imaging and blood oxygen saturation and oxygen metabolism rate based on photoacoustic imaging. This multimodal imaging system combining multiphoton and photoacoustic imaging can provide a more comprehensive understanding of the intrinsic connections within biological tissues, more accurately resolve complex concurrent medical problems, and provide stronger technical support for biomedical research.

[0005] Due to the different requirements of multiphoton imaging and photoacoustic imaging for the laser light source, current hybrid imaging systems based on multiphoton imaging and photoacoustic imaging all use two different light sources coupled together (Rao, B. et al. Integrated photoacoustic, confocal, and two-photon microscope. J. Biomed. Opt 19, 036002) before acting simultaneously. This has disadvantages such as large size, high cost, and system complexity, making it difficult to integrate (Song, W. et al. Fully integrated reflection-mode photoacoustic, two-photon and second harmonic generation microscopy in vivo. Sci Rep 6, 32240). Summary of the Invention

[0006] The problem that this invention aims to solve is that a single imaging mode has limited information dimensions.

[0007] The hybrid imaging system based on GHz repetition rate femtosecond pulse train proposed in this invention will provide a solution to the above problems. It performs multiphoton imaging and photoacoustic imaging simultaneously based on a femtosecond laser, and implements multi-dimensional real-time observation. Compared with the existing technology, it has the advantages of system integration and low cost.

[0008] The objective of this invention is achieved by at least one of the following technical solutions.

[0009] A multimodal imaging system based on radio frequency programmable GHz femtosecond pulse trains includes a femtosecond pulse laser source, a pulse splitting module, a pulse amplification module, a pulse compression module, an imaging module, an optical signal acquisition component, an ultrasonic signal acquisition component, and a data processing component;

[0010] The single-pulse laser generated by the femtosecond pulsed laser source enters the pulse splitting module through spatial optical coupling. The femtosecond pulse train generated by the pulse splitting module then enters the pulse amplification module and the pulse compression module for energy amplification and pulse width compression before entering the imaging module. The imaging module simultaneously performs multiphoton imaging and photoacoustic imaging. The output of the imaging module is connected to the input of the optical signal acquisition unit and the ultrasonic signal acquisition unit, respectively. The outputs of the optical signal acquisition unit and the ultrasonic signal acquisition unit are connected to the input of the data processing unit, respectively. The optical signal and ultrasonic signal generated by the imaging module enter the optical signal acquisition unit and the ultrasonic signal acquisition unit, respectively, forming an electrical signal that can be calculated and analyzed. The electrical signal is then sent to the data processing unit for processing to generate the imaging result.

[0011] The femtosecond pulsed laser source is used to generate single-pulse laser with a repetition frequency in the megahertz range;

[0012] The pulse splitting module is used to uniformly split a single femtosecond pulse into multiple femtosecond pulses to form a pulse train with an approximate nanosecond envelope, thereby meeting the requirements of photoacoustic imaging.

[0013] The pulse amplification module is used to adjust the laser energy to achieve the pulse energy required for imaging the sample;

[0014] The pulse compression module is used to compress the pulse width to meet the requirements of multiphoton imaging;

[0015] The imaging module is used to simultaneously perform multiphoton imaging and photoacoustic imaging;

[0016] The optical signal acquisition component is used to receive the optical signal obtained by multiphoton imaging excitation and convert it into an electrical signal that can be calculated and analyzed.

[0017] The ultrasonic signal acquisition component is used to receive ultrasonic signals obtained from acousto-optic imaging and convert them into electrical signals that can be calculated and analyzed.

[0018] The data processing component is used to process the electrical signals generated by the optical signal acquisition component and the ultrasonic signal acquisition component to obtain imaging results.

[0019] This invention generates programmable GHz femtosecond pulse trains, enabling simultaneous multiphoton imaging and photoacoustic imaging based on a single femtosecond laser.

[0020] Furthermore, the femtosecond pulsed laser source is an all-fiber femtosecond pulsed laser, which, as the initial light source, can emit pulsed lasers with a repetition frequency in the megahertz range suitable for biological imaging.

[0021] Furthermore, in the pulse splitting module, the input femtosecond laser pulse is split into a pulse train containing multiple femtosecond pulses. The nanosecond-level envelope of the pulse train formed by splitting a single femtosecond laser pulse can be used for photoacoustic imaging, and the several femtosecond-level pulses within the envelope can be used for multiphoton imaging.

[0022] Furthermore, the pulse splitting module includes a radio frequency signal generation component, an angle deviation component, a beam splitting and combining component, a relay optical path component, and a long mirror pair;

[0023] In the pulse splitting module, the signal from the radio frequency signal generation component acts on the angle deviation component, thereby splitting the input single femtosecond laser pulse into multiple laser beams with different deflection angles. These beams are then transmitted through the beam splitting and combining component to the relay optical path component. The relay optical path component relays the angle deviation generated by the angle deviation component to match the incident angle conditions of the long mirror pair. After multiple reflections by the long mirror pair, the laser beams with different deflection angles return to the original optical path to the beam splitting and combining component for output. The different optical path lengths of the lasers with different deflection angles in the long mirror pair create a uniform time delay, thus achieving the effect of pulse splitting. The number of deflection angles is consistent with the number of pulse splits. By programming the radio frequency signal loaded onto the angle deviation component, the number and intensity of the GHz femtosecond pulse train can be set in real time without changing the optical path system design. Therefore, the performance of the pulse train can be adjusted according to different imaging requirements to achieve the best imaging effect.

[0024] Furthermore, the radio frequency signal generating component includes a programmable terminal, an arbitrary waveform generator, and a radio frequency signal amplifier;

[0025] The programmable terminal controls an arbitrary waveform generator to send the required radio frequency signal, which is then amplified by the radio frequency signal amplifier and applied to the angle deviation component.

[0026] Furthermore, the angle deviation component is an acousto-optic deflector.

[0027] Furthermore, the beam splitter and combiner is a 50:50 beam splitter.

[0028] Furthermore, the pulse amplification module includes an all-fiber amplifier for amplifying the power of the split pulse train.

[0029] Furthermore, the pulse compression module is a dispersion-compensated fiber, which compresses the pulse width through dispersion compensation.

[0030] Furthermore, the imaging module includes a lens, an objective lens, a dichroic mirror, and a sample; after being collimated by the lens, the pulsed light is transmitted through the dichroic mirror and focused onto the sample by the objective lens; the light signal emitted by the sample returns to the dichroic mirror and is reflected and output.

[0031] Compared with existing technologies, the beneficial effects of the present invention are as follows:

[0032] 1. This invention utilizes pulse splitting technology to split a single femtosecond pulse into multiple femtosecond pulse trains and simulates nanosecond pulses through pulse envelopes. By adjusting the radio frequency signal loaded on the pulse splitting module, the number of pulses and pulse intensity of a GHz femtosecond pulse train can be designed in real time.

[0033] 2. This invention uses a single laser light source to simultaneously meet the requirements of photoacoustic imaging and multiphoton imaging, realizing a multimodal imaging system capable of simultaneously performing multiphoton imaging and photoacoustic imaging. Attached Figure Description

[0034] Figure 1 is a schematic diagram of the structure of a multimodal imaging system based on a radio frequency programmable GHz femtosecond pulse train in an embodiment of the present invention;

[0035] Figure 2 is a schematic diagram of the structure of the pulse-division module in an embodiment of the present invention;

[0036] Figure 3 is a schematic diagram of the pulse division principle in an embodiment of the present invention. Embodiments of the present invention

[0037] The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention.

[0038] Example:

[0039] A multimodal imaging system based on radio frequency programmable GHz femtosecond pulse train, as shown in Figure 1, includes a femtosecond pulse laser source 101, a pulse splitting module 102, a pulse amplification module 103, a pulse compression module 104, an imaging module 105, an optical signal acquisition component 106, an ultrasonic signal acquisition component 107, and a data processing component 108.

[0040] The single-pulse laser generated by the femtosecond pulse laser source 101 enters the pulse splitting module 102 through spatial optical coupling. The femtosecond pulse train generated by the pulse splitting module 102 then enters the pulse amplification module 103 and the pulse compression module 104 for energy amplification and pulse width compression before entering the imaging module 105. The imaging module 105 simultaneously performs multiphoton imaging and photoacoustic imaging. The output of the imaging module 105 is connected to the input of the optical signal acquisition component 106 and the ultrasonic signal acquisition component 107, respectively. The outputs of the optical signal acquisition component 106 and the ultrasonic signal acquisition component 107 are connected to the input of the data processing component 110, respectively. The optical signal and ultrasonic signal generated by the imaging module 105 enter the optical signal acquisition component 106 and the ultrasonic signal acquisition component 107, respectively, to form an electrical signal that can be calculated and analyzed. The electrical signal is then sent to the data processing component 108 for processing to generate the imaging result.

[0041] Currently, the mainstream multiphoton imaging includes two-photon imaging and three-photon imaging. Depending on the specific requirements of medical imaging, the two-photon-photoacoustic hybrid imaging mode or the three-photon-photoacoustic hybrid imaging mode can be selected by setting the working wavelength of the laser.

[0042] In this embodiment, the three-photon-photoacoustic hybrid imaging mode is taken as an example.

[0043] The femtosecond pulsed laser source 101 is a 1700nm all-fiber femtosecond pulsed laser with an average output laser power of up to 5W, a pulse repetition frequency of 1MHz, and a pulse width of 100fs. As an initial light source, it can emit pulsed lasers with a repetition frequency in the megahertz range suitable for biological imaging.

[0044] As shown in Figure 2, in the pulse splitting module 102, the input femtosecond laser pulse is split into a pulse train containing multiple femtosecond pulses. The nanosecond-level envelope of the pulse train formed by splitting a single femtosecond laser pulse can be used for photoacoustic imaging, and the several femtosecond-level pulses within the envelope can be used for multiphoton imaging.

[0045] As shown in Figure 2, the pulse splitting module 102 includes a radio frequency signal generating component 201, an angle deviation component 202, a beam splitting and combining component 203, a relay optical path component 204, and a long mirror pair 205.

[0046] In the pulse splitting module 102, the signal from the radio frequency signal generation component 201 acts on the angle deviation component 202, thereby splitting the input single femtosecond laser pulse into multiple laser beams with different deflection angles. These beams are then transmitted through the beam splitting and combining component 203 to the relay optical path component 204. The relay optical path component 204 relays the angle deviation generated by the angle deviation component 202 to match the incident angle condition of the long mirror pair 205. After multiple reflections by the long mirror pair 205, the laser beams with different deflection angles return to the original optical path to the beam splitting and combining component 203 for output. Because the lasers with different deflection angles have different optical path lengths in the long mirror pair 205, a uniform time delay is generated, thereby achieving the effect of pulse splitting. The number of deflection angles is consistent with the number of pulse splits. By programming the radio frequency signal loaded onto the angle deviation component 202, the number of pulses and pulse intensity of the GHz femtosecond pulse train can be set in real time without changing the optical path system design. Therefore, the performance of the pulse train can be adjusted according to different imaging requirements to achieve the best imaging effect.

[0047] In one embodiment, the radio frequency signal generating component 201 includes a programmable terminal, an arbitrary waveform generator, and a radio frequency signal amplifier;

[0048] The programmable terminal controls the arbitrary waveform generator to send the required radio frequency signal, which is then amplified by the radio frequency signal amplifier and applied to the angle deviation component 202.

[0049] In one embodiment, the angle deflection component 202 is an acousto-optic deflector.

[0050] In one embodiment, the beam splitter and combiner 203 is a 50:50 beam splitter.

[0051] In one embodiment, the relay optical path component 204 includes a relay lens and a reflector; the long mirror pair 205 is a free-space angle linear frequency modulated pulse enhancement delay mirror pair. The pulse splitting module 102 splits a single laser pulse with a time interval of T1 = 1 μs into 21 sub-pulses with a time interval of T2 = 0.5 ns in the time domain. The number of sub-pulses can be controlled and deflected by designing a radio frequency signal loaded on the acousto-optic deflector to control the direction of the beam.

[0052] Figure 3 shows a schematic diagram of pulse splitting in this embodiment. The radio frequency signal designed by the programmable terminal is amplified by the radio frequency signal amplifier and then loaded onto the acousto-optic deflector. After passing through the acousto-optic deflector, the light beam is divided into 21 sub-beams with different deflection angles. The sub-beams pass through a 50:50 beam splitter. 50% of the light passes through the relay optical path component to relay the angle deviation caused by the angle deviation component to match the incident angle condition of the long mirror pair. After multiple reflections by the long mirror pair, the laser beams with different deflection angles return to the original optical path to the beam splitting and combining component for output. Due to the different optical path lengths of the lasers with different deflection angles in the long mirror, a uniform time delay T2 = 0.5 ns is generated, thereby achieving the effect of pulse splitting. When the beam is reflected back to the beam splitter, 50% of the light is output. A single pulse with a single pulse energy of E1 = 5 μJ is split in the time domain after passing through the pulse splitting module 102, forming a pulse train consisting of 21 sub-pulses with a time interval of T2. The beam has a diffraction efficiency of about 70% after passing through the AOD, about 50% after passing through the beam splitter and entering the relay module. The loss between the relay module and the high reflectivity long mirror pair is estimated to be 2dB. Finally, about 50% of the beam is output after passing through the beam splitter. The output optical power is increased by 13dB after passing through the pulse amplification module (103). The single pulse energy E2 of the final output pulse train is about 520nJ, and the single envelope pulse energy E3 is about 11μJ.

[0053] In one embodiment, the envelope consisting of a pulse train of 21 sub-pulses has a duration of 10 ns, a sub-pulse repetition rate F1 = 2 GHz, and an envelope pulse frequency F2 = 1 MHz. The pulse energy E2 and repetition rate F1 of the sub-pulses under the envelope meet the light source requirements for three-photon imaging, while the pulse energy E3 and repetition rate F2 of the envelope pulse meet the light source requirements for acousto-optic imaging.

[0054] In one embodiment, the pulse amplification module 103 is an all-fiber amplifier used to amplify the power of the split pulse train.

[0055] In one embodiment, the pulse compression module 104 is a dispersion compensation fiber, used to compensate for the dispersion caused by the gain fiber in the pulse amplifier, thereby achieving the effect of pulse width compression. After passing through the pulse compression module, the sub-pulse width in the envelope is 100 fs, and the envelope pulse duration is 10 ns, which respectively meet the pulse width requirements of three-photon imaging and photoacoustic imaging.

[0056] In one embodiment, the imaging module 105 includes a lens, an objective lens, a dichroscope, and a sample; the light acquisition component 106 is a photomultiplier tube; and the ultrasonic acquisition component 107 includes an ultrasonic detector, a signal amplifier, and an oscilloscope. The laser beam is shaped by two lenses and then focused onto the sample by the objective lens for imaging. Fluorescent signal light excited by three-photon absorption is incident on the photomultiplier tube through the dichroscope, thereby converting the optical signal into an electrical signal which is sent to the data processing component 108 for data analysis. The ultrasonic signal generated by photoacoustic imaging is collected by the ultrasonic detector, converted into an electrical signal by the oscilloscope, amplified by the signal amplifier, and then sent to the data processing component for data analysis to obtain a final high-resolution, multi-contrast biological image.

[0057] The above embodiments are one of the implementation methods of the present invention, but the implementation methods of the present invention are not limited to the embodiments and test examples. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. [Amended according to Rule 26, 26.09.2025] A multimodal imaging system based on radio frequency programmable GHz femtosecond pulse trains, characterized in that, It includes a femtosecond pulse laser source (101), a pulse splitting module (102), a pulse amplification module (103), a pulse compression module (104), an imaging module (105), an optical signal acquisition component (106), an ultrasonic signal acquisition component (107), and a data processing component (108); The single-pulse laser generated by the femtosecond pulse laser source (101) enters the pulse splitting module (102) through spatial optical coupling. The femtosecond pulse train generated by the pulse splitting module (102) enters the pulse amplification module (103) and pulse compression module (104) in sequence for energy amplification and pulse width compression before entering the imaging module (105). The imaging module (105) performs multiphoton imaging and photoacoustic imaging simultaneously. The output end of the imaging module (105) is connected to the input end of the optical signal acquisition component (106) and the ultrasonic signal acquisition component (107), respectively. The output ends of the optical signal acquisition component (106) and the ultrasonic signal acquisition component (107) are connected to the input end of the data processing component (110), respectively. The optical signal and ultrasonic signal generated by the imaging module (105) enter the optical signal acquisition component (106) and the ultrasonic signal acquisition component (107), respectively, to form an electrical signal. The electrical signal is sent to the data processing component (108) for processing to generate the imaging result.

2. The multimodal imaging system based on a radio frequency programmable GHz femtosecond pulse train according to claim 1, characterized in that: The femtosecond pulsed laser source (101) is an all-fiber femtosecond pulsed laser. As an initial light source, it can emit pulsed lasers with a repetition frequency of megahertz, suitable for biological imaging.

3. The multimodal imaging system based on a radio frequency programmable GHz femtosecond pulse train according to claim 1, characterized in that: In the pulse splitting module (102), the input femtosecond pulse laser is split into a pulse train containing multiple femtosecond pulses. The nanosecond-level envelope of the pulse train formed by splitting a single femtosecond pulse laser is used for photoacoustic imaging, and the envelope contains several femtosecond-level pulses used for multiphoton imaging.

4. A multimodal imaging system based on a radio frequency programmable GHz femtosecond pulse train according to claim 3, characterized in that: The pulse splitting module (102) includes a radio frequency signal generating component (201), an angle deviation component (202), a beam splitting and combining component (203), a relay optical path component (204), and a long mirror pair (205). In the pulse splitting module (102), the signal from the radio frequency signal generating component (201) acts on the angle deviation component (202), thereby splitting the input single femtosecond pulse laser into multiple laser beams with different deflection angles. These beams are then transmitted through the beam splitting and combining component (203) to the relay optical path component (204). The relay optical path component (204) relays the angle deviation generated by the angle deviation component (202) to match the incident angle conditions of the long mirror pair (205). After multiple reflections by the long mirror pair (205), the laser beams with different deflection angles return to the original optical path to the beam splitting and combining component (203) for output.

5. A multimodal imaging system based on a radio frequency programmable GHz femtosecond pulse train according to claim 4, characterized in that: The radio frequency signal generating component (201) includes a programmable terminal, an arbitrary waveform generator, and a radio frequency signal amplifier; The programmable terminal controls the arbitrary waveform generator to send the required radio frequency signal, which is then amplified by the radio frequency signal amplifier and applied to the angle deviation component (202).

6. A multimodal imaging system based on a radio frequency programmable GHz femtosecond pulse train according to claim 4, characterized in that: The angle deviation component (202) is an acousto-optic deflector.

7. A multimodal imaging system based on a radio frequency programmable GHz femtosecond pulse train according to claim 4, characterized in that: The beam splitter and combiner component (203) is a 50:50 beam splitter.

8. The multimodal imaging system based on a radio frequency programmable GHz femtosecond pulse train according to claim 1, characterized in that: The pulse amplification module (103) includes an all-fiber amplifier for amplifying the power of the split pulse train.

9. A multimodal imaging system based on a radio frequency programmable GHz femtosecond pulse train according to claim 1, characterized in that: The pulse compression module (104) is a dispersion-compensated fiber, which compresses the pulse width through dispersion compensation.

10. A multimodal imaging system based on a radio frequency programmable GHz femtosecond pulse train according to claim 1, characterized in that: The imaging module (105) includes a lens, an objective lens, a dichroic mirror, and a sample; after being collimated by the lens, the pulsed light is transmitted through the dichroic mirror and focused onto the sample by the objective lens; the light signal emitted by the sample returns to the dichroic mirror and is reflected and output.

Images