Multi-photon photoacoustic imaging system and method

Abstract

The invention discloses a multiphoton photoacoustic imaging system and method, and belongs to the technical field of photoacoustic imaging, the multiphoton photoacoustic imaging system comprises a laser, the laser is connected with a light beam scanning subsystem, the light beam scanning subsystem is connected with a multiphoton photoacoustic subsystem, the multiphoton photoacoustic subsystem is connected with an ultrasonic transducer, the ultrasonic transducer is connected with an image reconstruction system, and the image reconstruction system is connected with a light source. The light beam scanning subsystem comprises a laser convergence element and a light beam scanning element, and the multi-photon photoacoustic subsystem comprises an imaging target and an ultrasonic coupling agent; and the light beam scanning element enables the light spot of the pulse laser emitted by the laser device and the imaging target to generate relative motion and is used for realizing point-by-point scanning on the surface or inside the imaging target and exciting different areas of the imaging target to generate ultrasound. The multi-photon photoacoustic imaging system and method provided by the invention are used for realizing photoacoustic imaging, can break through the diffraction limit of light, and realize the improvement of the transverse and longitudinal resolution of photoacoustic imaging.

Description

Technical Field

[0001] This invention relates to the field of photoacoustic imaging technology, and in particular to a multiphoton photoacoustic imaging system and method. Background Technology

[0002] Photoacoustic imaging is a non-invasive imaging technique that uses ultrafast lasers to induce ultrasound waves in the target, which are then detected by an ultrasonic transducer to reconstruct a two-dimensional or three-dimensional image of the target. Employing a point-by-point scanning method, photoacoustic imaging can achieve highly detailed visualization of the target. It is currently widely used in the diagnosis, monitoring, and minimally invasive intervention of superficial tissues, playing an increasingly important role in both medical and scientific research.

[0003] Despite the significant advancements and widespread applications of photoacoustic imaging technology, traditional methods, which rely on single-photon absorption to generate ultrasound, are limited by fundamental physical laws. The size of the focused laser spot cannot exceed the diffraction limit. Therefore, photoacoustic imaging systems using existing technology face a bottleneck in imaging resolution, preventing further improvements. Summary of the Invention

[0004] The purpose of this invention is to provide a multiphoton photoacoustic imaging system and method to solve the problems existing in the background art.

[0005] To achieve the above objectives, the present invention provides a multiphoton photoacoustic imaging system, including a laser, the laser being connected to a beam scanning subsystem, the beam scanning subsystem being connected to a multiphoton photoacoustic subsystem, the multiphoton photoacoustic subsystem being connected to an ultrasonic transducer, the ultrasonic transducer being connected to an image reconstruction system, the beam scanning subsystem including a laser converging element and a beam scanning element, and the multiphoton photoacoustic subsystem including an imaging target and an ultrasonic coupling agent; The beam scanning element causes the spot of the pulsed laser emitted by the laser to move relative to the imaging target, thereby enabling point-by-point scanning on or inside the imaging target and exciting different regions of the imaging target to generate ultrasound.

[0006] Preferably, the imaging target is immersed in the ultrasound coupling agent.

[0007] Preferably, the laser emits a pulsed laser.

[0008] Preferably, after the pulsed laser is focused by the laser focusing element to form a light spot, at the edge of the light spot, the light intensity is lower than the multiphoton absorption threshold of the imaging target, and the imaging target is transparent to the pulsed laser; at the center of the light spot, the light intensity is higher than the multiphoton absorption threshold of the imaging target, and the imaging target absorbs the light energy, generates a thermoelastic effect, and excites an ultrasonic signal.

[0009] Preferably, the ultrasonic transducer is used to detect ultrasound induced by laser during multiphoton absorption and to convert the ultrasonic signal into an electrical signal.

[0010] Preferably, the image reconstruction subsystem is used to reconstruct a two-dimensional or three-dimensional image of the imaging target based on the electrical signal output by the ultrasonic transducer.

[0011] Preferably, the beam scanning subsystem is a laser scanning galvanometer.

[0012] Preferably, the beam scanning subsystem is a displacement stage.

[0013] A multiphoton photoacoustic imaging method includes the following steps: S1. The laser emitted by the laser is focused by the laser focusing element, and the focused light spot is incident on the imaging target. S2. Immerse the imaging target and ultrasonic transducer in the ultrasonic coupling agent; S3. Using the beam scanning subsystem, the laser spot scans the surface and interior of the imaging target; S4. At the edge of the laser spot, the light intensity is lower than the multiphoton absorption threshold of the imaging target. The imaging target is transparent to the pulsed laser and cannot generate ultrasound. S5. At the center of the laser spot, the light intensity is greater than the multiphoton absorption threshold of the imaging target. The imaging target absorbs the light energy, generates a thermoelastic effect, and excites an ultrasonic signal. S6. Use an ultrasonic transducer to detect ultrasound generated by multiphoton absorption in the imaging target; S7. Reconstruct the image of the target based on the output signal of the ultrasonic transducer.

[0014] Therefore, the multiphoton photoacoustic imaging system and method described above have the following beneficial effects: (1) By using the multiphoton absorption process to excite ultrasonic signals, photoacoustic imaging can be achieved, which can break through the diffraction limit of light and improve the horizontal and vertical resolution of photoacoustic imaging. (2) The horizontal resolution is improved to the level of 10 nanometers to sub-100 nanometers, breaking through the difficulties faced by traditional photoacoustic imaging technology.

[0015] The technical solution of the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. Attached Figure Description

[0016] Figure 1 This is a schematic diagram of a multiphoton photoacoustic imaging system according to an embodiment of the present invention; Figure 2 This invention provides a multiphoton photoacoustic imaging system that uses a laser scanning galvanometer as the beam scanning system in an embodiment of the invention. Figure 3 This invention provides a multiphoton photoacoustic imaging system that uses a displacement stage as a beam scanning system in an embodiment of the invention. Figure 4 This is a schematic diagram illustrating the principle of multiphoton photoacoustic imaging that breaks the diffraction limit in an embodiment of the present invention; Figure 5 This is a schematic diagram of the light field distribution in the xoz plane of the focal region when a pulsed laser with a wavelength of 800 nm is focused by an objective lens with a numerical aperture of 1.2, according to an embodiment of the present invention. Detailed Implementation

[0017] The following detailed description of embodiments of the invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the invention without inventive effort are within the scope of protection of the invention.

[0018] Please see Figure 1 A multiphoton photoacoustic imaging system includes a laser, a beam scanning subsystem connected to the laser, a multiphoton photoacoustic subsystem connected to the beam scanning subsystem, an ultrasonic transducer connected to the multiphoton photoacoustic subsystem, an image reconstruction system connected to the ultrasonic transducer, the beam scanning subsystem including a laser converging element and a beam scanning element, and the multiphoton photoacoustic subsystem including an imaging target and an ultrasonic coupling agent. A beam scanning element causes the spot of the pulsed laser emitted by the laser to move relative to the imaging target, thereby enabling point-by-point scanning on or inside the imaging target and exciting different regions of the imaging target to generate ultrasound.

[0019] The laser is a pulsed laser, which can be a femtosecond laser or a picosecond laser.

[0020] The imaging target is immersed in an ultrasonic coupling agent. The ultrasonic coupling agent is transparent to the laser light emitted by the laser.

[0021] At the edge of the laser spot, the intensity of the pulsed laser is lower than the multiphoton absorption threshold of the target, making the target transparent to the pulsed laser. At the center of the laser spot, the intensity is higher than the multiphoton absorption threshold of the target, causing the target to absorb the light energy, generate a thermoelastic effect, and excite an ultrasonic signal.

[0022] An ultrasonic transducer is used to detect ultrasound induced by laser during multiphoton absorption and converts the ultrasonic signal into an electrical signal.

[0023] The image reconstruction subsystem is used to reconstruct two-dimensional or three-dimensional images of an imaging target based on the electrical signals output by the ultrasonic transducer.

[0024] Example 1 like Figure 2 The system includes a laser, which is connected to a beam scanning subsystem. The beam scanning subsystem is connected to a multiphoton photoacoustic subsystem, which is connected to an ultrasonic transducer. The ultrasonic transducer is connected to an image reconstruction system. The beam scanning subsystem is a laser scanning galvanometer. Based on the laser scanning galvanometer, the pulsed laser spot is moved and scanned on the target sample to be imaged, thereby achieving point-by-point scanning on the surface or inside of the target.

[0025] Example 2 like Figure 3 The system includes a laser, a beam scanning subsystem connected to the laser, a multiphoton photoacoustic subsystem connected to the multiphoton photoacoustic subsystem, an ultrasonic transducer connected to the multiphoton photoacoustic subsystem, and an image reconstruction system connected to the ultrasonic transducer. The beam scanning subsystem is a displacement stage. Based on the movement of the displacement stage, the target sample to be imaged moves relative to the spot of the pulsed laser, thereby achieving point-by-point scanning on the surface or inside of the target.

[0026] A multiphoton photoacoustic imaging method: A pulsed laser is incident on the imaging target. At the edge of the laser spot, the light intensity is weak, and the imaging target does not absorb it, thus remaining transparent to the pulsed laser. At the center of the laser spot, the light intensity exceeds the multiphoton absorption threshold of the imaging target. The imaging target absorbs the light energy, generating a thermoelastic effect that excites ultrasonic signals. These ultrasonic signals are received by an ultrasonic transducer, and after reconstruction, the image information of the imaging target can be obtained. For the laser spot, the smaller the area where the light intensity exceeds the multiphoton absorption threshold of the imaging target, the smaller the area where the imaging target emits ultrasound, which is more conducive to obtaining high imaging resolution.

[0027] The working principle of this embodiment is as follows: The converged pulsed laser light is incident on the imaging target. At the edge of the laser spot, the light intensity is weak, and the imaging target does not absorb the laser, thus remaining transparent to the pulsed laser and unable to generate ultrasound. At the center of the laser spot, the laser intensity exceeds the multiphoton absorption threshold of the imaging target, causing the target to absorb the light energy, generating a thermoelastic effect and exciting ultrasonic signals. These ultrasonic signals are received by an ultrasonic transducer, and after reconstruction, the image information of the imaging target can be obtained. Figure 4 , Figure 5 As shown, the effective diameter of the spot capable of exciting ultrasonic signals d 0, much smaller than the actual diameter of the converged light spot. d 1. Therefore, multiphoton photoacoustic systems can break through the diffraction limit. A schematic diagram illustrating the principle of multiphoton photoacoustic imaging that breaks the diffraction limit, as shown below. Figure 4 As shown, where xThe axis is perpendicular to the optical axis of the laser focusing element. After the laser is focused, the spot diameter is... d 1. At the edge of the light spot, the light intensity is lower than the multiphoton absorption threshold of the imaging target. I 0, therefore the imaging target is transparent to the laser and cannot generate ultrasound; at the center of the laser spot, the light intensity is greater than the multiphoton absorption threshold of the imaging target. I 0. The imaging target absorbs light energy, generating a thermoelastic effect that excites ultrasonic signals. For a converging laser spot, the effective diameter of the laser spot capable of exciting ultrasonic signals is... d 0. From Figure 4 It can be seen that, d 0 much smaller d 1. Therefore, multiphoton photoacoustic systems can break through the diffraction limit.

[0028] To further illustrate the above embodiments, water was selected as the ultrasonic coupling agent, the objective lens as the laser focusing element, and the imaging target as a quartz glass material. An 800 nm pulsed laser was focused by an objective lens with a numerical aperture of 1.2, and the image was concentrated in the focal region. xoz In-plane light field distribution as Figure 5 As shown, the x-axis is perpendicular to the optical axis of the objective lens, and the z-axis is along the optical axis of the objective lens. The focused laser beam has a spot diameter of... d At a wavelength of 547 nm, under the threshold effect of multiphoton absorption, only the spot region with a relative light intensity greater than 0.95 can excite ultrasonic signals, thus limiting the effective diameter of the laser spot. d 0 is only 86 nm. It can be seen that... d 0 is much smaller than d 1. Multiphoton photoacoustic imaging systems can overcome the influence of the diffraction limit.

[0029] Therefore, the present invention employs the above-described multiphoton photoacoustic imaging system and method, and adopts the multiphoton photoacoustic imaging system and method of the embodiments of the present invention described above in conjunction with the accompanying drawings. It utilizes the multiphoton (greater than or equal to two-photon) effect to induce ultrasound in the imaging target, and then uses an ultrasonic transducer to detect the ultrasound, thereby reconstructing a two-dimensional or three-dimensional super-resolution image of the imaging target, breaking through the diffraction limit of light, and solving the problems existing in the prior art.

[0030] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit them. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can still be made to the technical solutions of the present invention, and these modifications or equivalent substitutions cannot cause the modified technical solutions to deviate from the spirit and scope of the technical solutions of the present invention.

Claims

1. A multiphoton photoacoustic imaging system, characterized in that: The system includes a laser connected to a beam scanning subsystem, which is connected to a multiphoton photoacoustic subsystem. The multiphoton photoacoustic subsystem is connected to an ultrasonic transducer, which is connected to an image reconstruction system. The beam scanning subsystem includes a laser converging element and a beam scanning element. The multiphoton photoacoustic subsystem includes an imaging target and an ultrasonic coupling agent. The beam scanning element causes the spot of the pulsed laser emitted by the laser to move relative to the imaging target, thereby enabling point-by-point scanning on or inside the imaging target and exciting different regions of the imaging target to generate ultrasound.

2. The multiphoton photoacoustic imaging system according to claim 1, characterized in that: The imaging target is immersed in the ultrasound coupling agent.

3. The multiphoton photoacoustic imaging system according to claim 2, characterized in that: The laser emits pulsed laser light.

4. A multiphoton photoacoustic imaging system according to claim 3, characterized in that: After the pulsed laser is focused by the laser focusing element, it forms a light spot. At the edge of the light spot, the light intensity is lower than the multiphoton absorption threshold of the imaging target, and the imaging target is transparent to the pulsed laser. At the center of the light spot, the light intensity is higher than the multiphoton absorption threshold of the imaging target, and the imaging target absorbs the light energy, generates a thermoelastic effect, and excites an ultrasonic signal.

5. A multiphoton photoacoustic imaging system according to claim 4, characterized in that: The ultrasonic transducer is used to detect laser-induced ultrasound during multiphoton absorption and converts the ultrasonic signal into an electrical signal.

6. A multiphoton photoacoustic imaging system according to claim 5, characterized in that: The image reconstruction subsystem is used to reconstruct a two-dimensional or three-dimensional image of the imaging target based on the electrical signal output by the ultrasonic transducer.

7. A multiphoton photoacoustic imaging system according to claim 6, characterized in that: The beam scanning subsystem is a laser scanning galvanometer.

8. A multiphoton photoacoustic imaging system according to claim 6, characterized in that: The beam scanning subsystem is a displacement stage.

9. A multiphoton photoacoustic imaging method, using a multiphoton photoacoustic imaging system as described in any one of claims 1-8, characterized in that, Includes the following steps: S1. The laser emitted by the laser is focused by the laser focusing element, and the focused light spot is incident on the imaging target. S2. Immerse the imaging target and ultrasonic transducer in the ultrasonic coupling agent; S3. Using the beam scanning subsystem, the laser spot scans the surface and interior of the imaging target; S4. At the edge of the laser spot, the light intensity is lower than the multiphoton absorption threshold of the imaging target. The imaging target is transparent to the pulsed laser and cannot generate ultrasound. S5. At the center of the laser spot, the light intensity is greater than the multiphoton absorption threshold of the imaging target. The imaging target absorbs the light energy, generates a thermoelastic effect, and excites an ultrasonic signal. S6. Use an ultrasonic transducer to detect ultrasound generated by multiphoton absorption in the imaging target; S7. Reconstruct the image of the target based on the output signal of the ultrasonic transducer.

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