Photoacoustic imaging probe and imaging system

Abstract

The utility model belongs to the technical field of acousto-optic imaging, and particularly relates to a photoacoustic imaging probe and an imaging system. The optical fiber of the photoacoustic imaging probe and the photoacoustic imaging system can conduct exciting light into the outer tube, the exciting light is output from the other end of the outer tube through the gradient refractive index lens, the reflector, the MEMS galvanometer and the lens assembly and irradiates on a vascularized organoid, cells absorb light energy, instant elastic thermal expansion occurs, and the exciting light is radiated to the outside in an ultrasonic wave mode. An ultrasonic signal is reflected into the probe through the lens group and is received by the sensor, and then the signal is further processed and imaged; the probe does not need a complicated motor structure, so that imaging quality interference caused by external mechanical vibration is avoided, and the complexity of a system structure is greatly simplified; according to the present invention, the endogenous absorption of hemoglobin is adopted to perform imaging, such that the contrast does not need to be provided by other means such as dyeing, the method is the safe and non-invasive means, and the vascularized organ can be observed for a long time.

Description

Technical Field

[0001] The utility model belongs to the technical field of acousto-optic imaging, and in particular relates to a photoacoustic imaging probe and an imaging system. Background Art

[0002] The special culture environment of organoids places high demands on imaging. The current mainstream imaging method is optical imaging technology such as confocal imaging. This purely optical imaging method lacks imaging depth and cannot provide functional information. Observation of specific cell structures and molecules also requires staining or labeling, which will affect the physiological state of the organoids.

[0003] Photoacoustic imaging is a non-invasive, radiation-free, non-ionizing and safe imaging technology that combines the advantages of optical imaging and acoustic imaging, and can provide high imaging contrast at the cellular level and a large penetration depth. In addition, by combining multiple wavelengths, it can also provide functional information such as blood oxygen saturation and blood flow velocity, thereby revealing more disease information about human tissues and organs. However, there is currently no imaging system with related technology to image organoids. Utility Model Content

[0004] The utility model aims to provide a photoacoustic imaging probe and an imaging system, which facilitate non-invasive high-resolution functional imaging of vascularized organoids by constructing a miniaturized photoacoustic probe.

[0005] The present application provides a photoacoustic imaging probe. The photoacoustic imaging probe comprises: an outer tube, inside which a gradient refractive index lens, a reflector, a MEMS oscillator and a lens assembly are arranged; an optical fiber is inserted from one end of the outer tube, and is used to transmit excitation light to the gradient refractive index lens, and is output from the other end of the outer tube in sequence through the reflector, the MEMS oscillator and the lens assembly; a sensor is arranged in the outer tube, and is used to receive an ultrasonic signal reflected by the lens assembly.

[0006] In one embodiment of the present application, a quartz tube is disposed inside the outer tube; a gradient refractive index lens is fixed inside one end of the quartz tube, and a capillary is fixed inside the other end; and the end of the optical fiber is fixed in the capillary.

[0007] In one embodiment of the present application, the outer tube is a sheath tube; the outer diameter of the outer tube is 3 mm.

[0008] In one embodiment of the present application, the distance between the optical fiber and the end face of the gradient refractive index lens is 0.4 mm.

[0009] In one embodiment of the present application, the optical fiber is a single-mode optical fiber.

[0010] In one embodiment of the present application, the lens assembly includes two right-angle prisms.

[0011] Accordingly, the present application provides an imaging system. The imaging system includes: a laser generating unit, a data acquisition module, a processing module, and the above-mentioned photoacoustic imaging probe; wherein the laser generating unit is connected to an optical fiber for emitting excitation light; the data acquisition module is connected to a sensor for receiving an ultrasonic signal acquired by the sensor; and the control module is electrically connected to the laser generating unit and the data acquisition module for controlling the laser source to emit pulsed light and receiving data acquired by the data acquisition module.

[0012] In one embodiment of the present application, the laser generating unit includes: a first laser for emitting laser light of a first wavelength; a second laser for emitting laser light of a second wavelength; and a dichroic mirror for combining the laser light of the first wavelength and the laser light of the second wavelength into the excitation light.

[0013] In one embodiment of the present application, the first wavelength is 515 nm; and the second wavelength is 532 nm.

[0014] The beneficial effects of the utility model are as follows: the optical fiber of the photoacoustic imaging probe and imaging system of the present application can transmit the excitation light into the outer tube, and output it from the other end of the outer tube through the gradient refractive index lens, the reflector, the MEMS galvanometer and the lens assembly, and irradiate it on the vascularized organoids. The cells absorb the light energy, undergo instantaneous elastic thermal expansion, and radiate to the outside in the form of ultrasonic waves. The ultrasonic signal is reflected into the probe through the lens group and received by the sensor, and then the signal is further processed and imaged. The probe does not require a complex motor structure, avoids imaging quality interference caused by external mechanical vibration, and greatly simplifies the complexity of the system structure. The endogenous absorption of hemoglobin is used for imaging, so there is no need for staining or other means to provide contrast. It is a safe and non-invasive means, and can be used for long-term observation of vascularized organoids. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] In order to more clearly illustrate the specific implementation methods of the utility model or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the utility model. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0016] Figure 1 It is a schematic diagram of a photoacoustic imaging probe of a preferred embodiment of the utility model;

[0017] Figure 2 is a schematic diagram of an imaging system according to a preferred embodiment of the present utility model;

[0018] Figure 3It is a schematic diagram of a laser generating unit of a preferred embodiment of the utility model;

[0019] Figure 4 is a schematic diagram of a lens assembly of a preferred embodiment of the utility model;

[0020] In the figure:

[0021] Outer tube 1, quartz tube 11, capillary 12, gradient refractive index lens 2, reflector 3, MEMS galvanometer 4, lens assembly 5, first right-angle prism 51, second right-angle prism 52, silicone oil layer 53, optical fiber 6, sensor 7. DETAILED DESCRIPTION

[0022] In order to make the purpose, technical solution and advantages of the embodiments of the utility model clearer, the technical solution of the utility model will be clearly and completely described below in conjunction with the accompanying drawings. Obviously, the described embodiments are part of the embodiments of the utility model, not all of the embodiments. Based on the embodiments of the utility model, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the utility model.

[0023] The present application provides a photoacoustic imaging probe and an imaging system, which are described in detail below. It should be noted that the description order of the following embodiments does not limit the preferred order of the embodiments of the present application. In the following embodiments, the description of each embodiment has its own emphasis. For parts that are not described in detail in a certain embodiment, please refer to the relevant description of other embodiments.

[0024] See also Figure 1 The first embodiment of the utility model provides a photoacoustic imaging probe, comprising: an outer tube 1, inside which a gradient refractive index lens 2, a reflector 3, a MEMS galvanometer 4 and a lens assembly 5 are arranged; an optical fiber 6, extending from one end of the outer tube 1, is used to transmit the excitation light to the gradient refractive index lens 2, and output from the other end of the outer tube 1 in sequence through the reflector 3, the MEMS galvanometer 4 and the lens assembly 5; a sensor 7, arranged in the outer tube 1, is used to receive the ultrasonic signal reflected by the lens assembly 5.

[0025] In this embodiment, optionally, the outer tube 1 is a sheath tube; the outer diameter of the outer tube 1 is 3 mm.

[0026] In this embodiment, the gradient refractive index lens 2 may be a G-lens lens; the sensor 7 may be a piezoelectric sensor.

[0027] In this embodiment, as an optional fixing method, a quartz tube 11 is arranged inside the outer tube 1; a gradient refractive index lens 2 is fixed at one end of the quartz tube 11, and a capillary 12 is fixed at the other end; the end of the optical fiber 6 is fixed in the capillary 12.

[0028] Specifically, during installation, the end face of the optical fiber 6 is cut flat and then inserted into the capillary and fixed with ultraviolet glue, and a gap is formed between the optical fiber 6 and the gradient refractive index lens 2; the optical fiber 6 and the gradient refractive index lens 2 are butt-coupled to converge the excitation light; next, the two are placed in a quartz tube and fixed in the outer tube 1.

[0029] In this embodiment, the focal length of the probe can be adjusted by controlling the distance between the end face of the optical fiber 6 and the gradient refractive index lens 2; preferably, the distance between the end face of the optical fiber 6 and the gradient refractive index lens 2 is 0.4 mm.

[0030] In this embodiment, optionally, the optical fiber 6 is a single-mode optical fiber.

[0031] See also Figure 4 As an optional embodiment, the lens assembly 5 includes two right-angle prisms, namely a first right-angle prism 51 and a second right-angle prism 52; a silicone oil layer 53 is coated between the inclined surfaces of the two right-angle prisms; the silicone oil has an optical refractive index similar to that of the lens but a different acoustic impedance characteristic, so the silicone oil layer 53 can penetrate the light beam and reflect the sound beam, thereby separating the laser from the ultrasound reflected back by the biological body.

[0032] See also Figure 2 On the basis of the above embodiments, the second aspect of the present invention provides an imaging system, comprising: a laser generating unit, a data acquisition module, a processing module, and the photoacoustic imaging probe as described above; wherein the laser generating unit is connected to the optical fiber 6 for emitting excitation light; the data acquisition module is connected to the sensor 7 for receiving the ultrasonic signal acquired by the sensor 7; the control module is electrically connected to the laser generating unit and the data acquisition module for controlling the laser source to emit pulsed light and receiving the data acquired by the data acquisition module.

[0033] In this embodiment, the data acquisition module may be a DAQ signal acquisition system, and the control module may be a PC. It should be noted that the PC may use existing technology to perform imaging based on the data acquired by the sensor 7 and the data acquisition module, which will not be described in detail here.

[0034] See also Figure 3 Optionally, the laser generating unit includes: a first laser for emitting laser light of a first wavelength; a second laser for emitting laser light of a second wavelength; and a dichroic mirror for combining the laser light of the first wavelength and the laser light of the second wavelength into the excitation light.

[0035] Preferably, the first wavelength is 515 nm; and the second wavelength is 532 nm.

[0036] In one application scenario, in order to achieve functional imaging such as blood oxygen saturation, a dual-wavelength of 532+515nm is used as a seed excitation source for photoacoustic excitation to generate an ultrasonic signal; blood oxygen saturation is determined based on the concentration ratio of aerobic and deoxygenated hemoglobin in the blood. Since aerobic and deoxygenated hemoglobin show large absorption differences in the optical absorption spectrum, that is, the absorption coefficients of the two for different light wavelengths are different, the appropriate dual-wavelength excitation light can be selected to measure blood oxygen saturation.

[0037] See also Figure 3 , where L1 is a reflector, L2 is an attenuator, and L3 is a dichroic mirror; the first laser and the second laser emit 515nm and 532nm lasers respectively, and then collimate them and combine them at L3. L3 transmits 532nm light and reflects 515nm light. The attenuator is used to adjust the energy of the optical path. The combined laser enters the optical fiber 6 in the probe after collimation.

[0038] See also Figure 1 and Figure 2 The excitation light is introduced into the probe through the optical fiber 6, focused by the G-lens, provided with a field of view by the MEMS galvanometer 4, and then emitted from the lens assembly 5 to irradiate the vascularized organoid. The cells absorb the light energy, undergo instantaneous elastic thermal expansion, and radiate to the outside world in the form of ultrasound. The ultrasonic signal is reflected into the probe through the lens assembly 5 and received by the piezoelectric sensor. The piezoelectric sensor outputs the received signal to the DAQ signal acquisition system for data acquisition, and performs corresponding filtering, amplification, and digital processing. The PC controls the synchronization of laser triggering and signal acquisition, and images the data.

[0039] In some application scenarios, the positioning of organoids is a major challenge for organoid imaging. Photoacoustic imaging usually uses an external motor to perform large-scale scanning imaging, and then gradually narrows the range to finally determine the target position. This is time-consuming and labor-intensive, and because mechanical structures such as motors will cause certain vibrations, thus affecting the imaging quality. Therefore, on the basis of the utility model, the positioning of organoids can be accurately achieved by combining an optical microscope with a micromanipulator. Specifically, the optical microscope can easily find the organoids in the multi-well plate or culture dish, and the micromanipulator can clamp the photoacoustic imaging probe of the utility model to provide three-dimensional precise positioning at the nm level, so it is easier to achieve precise positioning imaging of organoids.

[0040] In addition, deep imaging of organoids has always been a difficulty. Optical methods such as confocal microscopy have very limited penetration capabilities for cell accumulation exceeding a certain thickness. This penetration depth is usually only a few hundred microns, which makes it difficult to meet the three-dimensional imaging requirements of vascularized organoids. The photoacoustic imaging system constructed in the present invention benefits from the fact that the attenuation of acoustics in tissues is 2 to 3 orders of magnitude less than that of optics, and can provide a penetration depth of several millimeters.

[0041] Acquiring functional information of organoids is the development trend of organoid imaging. Currently, related imaging equipment can only track and observe certain molecules or substances through staining or labeling, which will affect the physiological activity of vascularized organoids. The photoacoustic imaging system constructed in the utility model uses the endogenous absorption of hemoglobin for imaging, so there is no need for staining or other means to provide contrast. It is a safe and non-invasive method that can be used for long-term observation of vascularized organoids.

[0042] The positioning of organoids is a time-consuming and laborious task. Therefore, based on the present invention, an optical microscope can be introduced as an auxiliary positioning of organoids. With the help of the optical microscope, the organoids in the culture dish or multi-well plate can be easily found, and then the probe can be clamped by the micromanipulator for precise positioning. The focus of the probe is controlled to be located on the surface of the organoid. The two-dimensional galvanometer can change the laser emission angle to image the organoids near the focus.

[0043] It should be noted that the various devices selected in this application (components whose specific structures are not described) are all universal standard parts or components known to technical personnel in this field, and their structures and principles can be known to technical personnel through technical manuals or through conventional experimental methods.

[0044] In the description of the embodiments of the present invention, unless otherwise clearly specified and limited, the terms "installed", "connected", and "connected" should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be the internal communication of two components. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0045] In the description of the present invention, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc., indicating the orientation or positional relationship, are based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore cannot be understood as limiting the present invention. In addition, the terms "first", "second", and "third" are used for descriptive purposes only, and cannot be understood as indicating or implying relative importance.

[0046] Based on the above ideal embodiments of the utility model, the relevant staff can make various changes and modifications without deviating from the technical concept of the utility model through the above description. The technical scope of the utility model is not limited to the content of the specification, and its technical scope must be determined according to the scope of the claims.

Claims

1. A photoacoustic imaging probe, characterized in that: include: An outer tube (1) having a gradient refractive index lens (2), a reflector (3), a MEMS galvanometer (4) and a lens assembly (5) arranged therein; An optical fiber (6) extends from one end of the outer tube (1) and is used to transmit the excitation light to the gradient refractive index lens (2), and then sequentially passes through the reflector (3), the MEMS galvanometer (4) and the lens assembly (5) to be output from the other end of the outer tube (1); The sensor (7) is arranged in the outer tube (1) and is used to receive the ultrasonic signal reflected by the lens assembly (5).

2. The photoacoustic imaging probe according to claim 1, characterized in that: A quartz tube (11) is arranged inside the outer tube (1); A gradient refractive index lens (2) is fixed in one end of the quartz tube (11), and a capillary tube (12) is fixed in the other end; The end of the optical fiber (6) is fixed in the capillary (12).

3. The photoacoustic imaging probe according to claim 1, characterized in that: The outer tube (1) is a sheath tube; The outer diameter of the outer tube (1) is 3 mm.

4. The photoacoustic imaging probe according to claim 1, characterized in that: The distance between the optical fiber (6) and the end face of the gradient refractive index lens (2) is 0.4 mm.

5. The photoacoustic imaging probe according to claim 1, characterized in that: The optical fiber (6) is a single-mode optical fiber.

6. The photoacoustic imaging probe according to claim 1, characterized in that: The lens assembly (5) comprises two right-angle prisms.

7. An imaging system, characterized in that: include: A laser generating unit, a data acquisition module, a processing module, and a photoacoustic imaging probe as claimed in any one of claims 1 to 6; in The laser generating unit is connected to the optical fiber (6) and is used to emit excitation light; The data acquisition module is connected to the sensor (7) and is used to receive the ultrasonic signal acquired by the sensor (7); The processing module is electrically connected to the laser generating unit and the data acquisition module, and is used to control the laser source to emit pulse light and receive data acquired by the data acquisition module.

8. The imaging system according to claim 7, characterized in that: The laser generating unit comprises: A first laser, configured to emit laser light of a first wavelength; A second laser configured to emit laser light of a second wavelength; and The dichroic mirror is used to combine the laser beams of the first wavelength and the second wavelength into the excitation light.

9. The imaging system according to claim 8, characterized in that The first wavelength is 515 nm; The second wavelength is 532 nm.

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