阅读说明：本技术 一种四模态光声、超声、荧光和光学成像显微镜系统 (Four-mode photoacoustic, ultrasonic, fluorescence and optical imaging microscope system ) 是由 杨斐 熊科迪 王志阳 王巍 陈钰盈 于 2021-08-04 设计创作，主要内容包括：本发明公开了一种四模态光声、超声、荧光和光学成像显微镜系统,包括光声、超声成像系统、荧光成像系统以及光学成像系统。所述光声、超声成像系统,包括超声换能器、物镜、二向色镜、准直器；激光经过准直器、二向色镜和物镜,超声换能器进行超声、光声信号采集；所述荧光成像系统,包括荧光拍摄相机、荧光光源；荧光光源照射样品产生激发光,透过二向色镜经过滤光片滤光,由荧光拍摄相机拍摄；所述光学成像系统,光源照射样品的像经物镜聚焦,移动反射镜反射由荧光拍摄相机接收。本发明能够同时或独立进行光声、超声扫描成像,荧光、光学成像可通过光路转换拍摄显像。切换成像模态无需调试,使四模态光声、超声、荧光和光学成像系统之间相互融合。(The invention discloses a four-mode photoacoustic, ultrasonic, fluorescence and optical imaging microscope system, which comprises a photoacoustic imaging system, an ultrasonic imaging system, a fluorescence imaging system and an optical imaging system. The photoacoustic and ultrasonic imaging system comprises an ultrasonic transducer, an objective lens, a dichroic mirror and a collimator; the laser passes through a collimator, a dichroic mirror and an objective lens, and an ultrasonic transducer is used for collecting ultrasonic and photoacoustic signals; the fluorescence imaging system comprises a fluorescence shooting camera and a fluorescence light source; the fluorescence light source irradiates the sample to generate exciting light, the exciting light passes through the dichroic mirror, is filtered by the optical filter and is shot by the fluorescence shooting camera; in the optical imaging system, an image of a sample irradiated by a light source is focused by an objective lens, and is reflected by a movable reflector and received by a fluorescence shooting camera. The invention can simultaneously or independently perform photoacoustic and ultrasonic scanning imaging, and fluorescence and optical imaging can be shot and developed through light path conversion. The imaging modes are switched without debugging, so that four-mode photoacoustic, ultrasonic, fluorescent and optical imaging systems are fused with each other.)

1. The photoacoustic and ultrasonic imaging system of the four-mode photoacoustic, ultrasonic, fluorescent and optical imaging microscope is characterized by comprising an ultrasonic transducer, an objective lens, a dichroic mirror, a collimator support and an optical fiber, wherein the collimator is fixed on the collimator support and connected with the optical fiber, laser required by photoacoustic imaging is introduced into a microscope body, and the laser is reflected by the dichroic mirror to enter the objective lens and the ultrasonic transducer. The optical path supports photoacoustic imaging.

2. A photoacoustic and ultrasound imaging system for a four-modality photoacoustic, ultrasound, fluorescence and optical imaging microscope according to claim 1, further comprising a connecting plate, a transition cube, the dichroic mirror being fixed on the transition cube above the objective lens, the transition cube, the objective lens being fixed coaxially above and below the connecting plate, ensuring the stability of photoacoustic and ultrasound imaging during scanning. The photoacoustic and ultrasonic scanning imaging can be simultaneously or independently carried out through the control of software on the host.

3. The fluorescence imaging system of the four-mode photoacoustic, ultrasonic, fluorescence and optical imaging microscope is characterized by further comprising an optical filter, a fluorescence light source and a fluorescence shooting camera, wherein the fluorescence light source irradiates a sample above the sample, the image of the sample is focused by an objective lens, is transmitted through a dichroic mirror of a conversion cube, is filtered through the optical filter and is shot by the fluorescence shooting camera, and the dichroic mirror, the optical filter and the fluorescence light source can be replaced according to a specific imaging marking probe.

4. The utility model provides a four modal optoacoustic, supersound, fluorescence and optical imaging microscope's optical imaging system, its characterized in that, includes that optics shoots camera, eyepiece, optical reflector support, optical reflector slide rail, optical reflector support screens, white light source, microscope shell, optics shoots camera and eyepiece and fixes on the microscope shell, optical reflector fixes on optical reflector support, optical reflector support fixes on optical reflector support slide rail, controls reciprocating of optical reflector, optical reflector support slide rail is fixed on microscope shell.

5. The optical imaging system of a four-mode photoacoustic, ultrasound, fluorescence and optical imaging microscope according to claim 4, further comprising a mirror, wherein when the optical mirror slide rail moves to the lower end, the dichroic mirror in the conversion cube is changed to be a mirror, the image of the totally reflected sample enters the eyepiece and the optical photographing camera, and when the optical mirror slide rail moves to the upper end, the image enters the photoacoustic, ultrasound or fluorescence mode.

6. The utility model provides a four modal optoacoustic, supersound, fluorescence and optical imaging microscope's light path conversion equipment, its characterized in that still includes two-dimentional electronic displacement platform, two-dimentional electronic displacement platform is fixed on the connecting plate, optoacoustic, supersound imaging system pass through two-dimentional electronic displacement platform scanning imaging, fluorescence, optical imaging system pass through fluorescence light source or white light source direct irradiation sample development.

Technical Field

The invention relates to the technical field of living small animal microscopes, in particular to a four-mode photoacoustic, ultrasonic, fluorescent and optical imaging microscope system for living small animals.

Background

The small animal is an important model for basic biomedical research, and plays an important role in simulating the physiological function of human beings, guiding the disease research of the human beings, exploring effective treatment means and the like. High spatial and temporal resolution observations of small animal models can provide detailed analysis of biological processes.

There are many methods of small animal imaging, and many small animal imaging systems utilize methods other than optical imaging, including magnetic resonance imaging, computed tomography, and the like. Although these techniques have some depth penetration, there are practical difficulties and problems, such as high cost and long acquisition time for magnetic resonance imaging; computed tomography imaging has certain safety risks.

The pure optical imaging has high resolution and high contrast to the imaging tissue, and the ultrasonic imaging has deeper penetration depth to the tissue and can reflect acoustic impedance parameters of the tissue. Fluorescence imaging may reflect certain specific attributes of a small living animal. The photoacoustic imaging is a novel nondestructive medical imaging technology, short pulse laser is used for irradiating a light absorption medium, the temperature of the light absorption medium is rapidly increased after the light absorption medium absorbs light energy, and the medium expands to generate mechanical waves, so that ultrasonic signals are generated, and the ultrasonic signals are called photoacoustic signals. The application develops the integrated research of the four-modal photoacoustic, ultrasonic, fluorescent and optical imaging microscope, develops the four-modal photoacoustic, ultrasonic, fluorescent and optical imaging microscope system, can reflect high-resolution information of the surface of a tissue, acoustic impedance parameters of the deep layer of the tissue and immune and fluorescent characteristics of small living animals, and can also reflect light absorption parameters of the tissue.

Disclosure of Invention

The invention aims to provide a four-mode photoacoustic, ultrasonic, fluorescent and optical imaging microscope system which has the functions of freely switching among four modes, independently imaging and simultaneously imaging, and quickly and accurately realizing imaging of different modes without complex adjustment.

The technical scheme is as follows:

a four-mode photoacoustic, ultrasonic, fluorescence and optical imaging microscope comprises an ultrasonic transducer, an objective lens, a dichroic mirror, a conversion cube, a collimator support and an optical fiber, wherein the collimator is fixed on the collimator support and connected with the optical fiber, laser is introduced into a microscope main body, the dichroic mirror is fixed on the conversion cube, and the laser introduced by the optical fiber is reflected to enter the objective lens and the ultrasonic transducer.

And the collimator support, the conversion cube and the objective lens are fixed on the connecting plate, so that the photoacoustic imaging and the ultrasonic imaging stability in the scanning process are ensured.

The dichroic mirror is positioned in the conversion cube, an image of a sample is irradiated by the fluorescent light source, the image is transmitted by the dichroic mirror of the conversion cube, filtered by the optical filter and shot by the fluorescence shooting camera, and the dichroic mirror, the optical filter and the fluorescent light source can be replaced according to a specific imaging marking probe.

The utility model provides a four modal optoacoustic, supersound, fluorescence and optical imaging microscope's optical imaging system, includes that optics shoot camera, eyepiece, optical reflector support, optical reflector slide rail, optical reflector support screens, white light source, microscope shell, optics shoot camera and eyepiece and fix on the microscope shell, the optical reflector is fixed on the optical reflector support, the optical reflector support is fixed on optical reflector support slide rail, controls reciprocating of optical reflector, optical reflector support slide rail is fixed on the microscope shell.

The optical imaging device further comprises a reflector, when the optical reflector slide rail moves to the lower end, the dichroic mirror in the conversion cube is changed into a reflector, the image of the total reflection sample enters the eyepiece and the optical shooting camera and is in an optical imaging mode, and when the optical reflector slide rail moves to the upper end, the image enters a photoacoustic mode, an ultrasonic mode or a fluorescence mode.

The utility model provides a light path conversion equipment of four modality optoacoustic, supersound, fluorescence and optical imaging microscope, includes two-dimentional electric displacement platform, two-dimentional electric displacement platform fixes on the connecting plate, optoacoustic, ultrasonic imaging system pass through two-dimentional electric displacement platform scanning imaging, fluorescence, optical imaging system pass through fluorescence light source or white light source direct irradiation sample development.

The invention has the following advantages and beneficial effects:

the four-mode photoacoustic, ultrasonic, fluorescence and optical imaging microscope system can realize simultaneous imaging of photoacoustic and ultrasonic and respectively realize photoacoustic, ultrasonic, fluorescence and optical imaging, wherein an optical imaging light path, a fluorescence imaging light path and a photoacoustic imaging light path are integrated together, the optical imaging mode and the photoacoustic imaging mode are controlled by the up-and-down movement of an optical reflector, the fluorescence imaging mode is realized by the replacement of a dichroic mirror and an optical filter, and the simultaneous or separate imaging of the photoacoustic imaging mode and the ultrasonic imaging mode is realized by the control of a background host software system.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this application, illustrate embodiments of the application and, together with the description, serve to explain the application and are not intended to limit the application.

FIG. 1 is a cross-sectional view of the overall structure of a four-mode photoacoustic, ultrasound, fluorescence and optical imaging microscope system;

FIG. 2 is an optical path diagram of a three-modality photoacoustic, ultrasound and optical imaging microscope system;

the system comprises an ultrasonic transducer 1, an objective lens 2, a dichroic mirror 3, a conversion cube 4, a collimator 5, a collimator support 6, an optical fiber 7, a connecting plate 8, an optical filter 9, a fluorescent light source 10, a fluorescent shooting camera 11, an optical shooting camera 12, an eyepiece 13, an optical reflector 14, an optical reflector support 15, an optical reflector slide rail 16, an optical reflector support clamping position 17, a white light source 18, a microscope shell 19, a two-dimensional electric displacement platform 20 and a sample 21.

Detailed Description

It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the disclosure. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.

It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments according to the present application. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, and it should be understood that when the terms "comprises" and/or "comprising" are used in this specification, they specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof, unless the context clearly indicates otherwise.

As introduced in the background art, the present invention is directed to a four-modality photoacoustic, ultrasound, fluorescence and optical imaging microscope system, which can be switched freely between four modalities, can be used for independent imaging and simultaneous imaging, does not require complex adjustment, and can rapidly and accurately realize imaging in different modalities.

In an exemplary embodiment of the present application, as shown in fig. 1, a four-mode photoacoustic, ultrasound, fluorescence and optical imaging microscope system includes an ultrasound transducer 1, an objective lens 2, a dichroic mirror 3, a conversion cube 4, a collimator 5, a collimator holder 6, an optical fiber 7. The collimator 5 is fixed on the collimator support 6 and connected with the optical fiber 7 to introduce laser into the microscope main body, the dichroic mirror 3 is fixed on the conversion cube 4 to reflect the introduced laser into the objective lens 2 and the ultrasonic transducer 1.

The photoacoustic and ultrasonic imaging system of the four-mode photoacoustic, ultrasonic and fluorescent optical imaging microscope further comprises a connecting plate 8, and the collimator support 6, the conversion cube 4 and the objective lens 2 are all fixed on the connecting plate 8, so that the photoacoustic and ultrasonic imaging stability in the scanning process is ensured.

As shown in fig. 1 and 2, the fluorescence imaging system of the four-mode photoacoustic, ultrasound, fluorescence and optical imaging microscope further includes a light filter 9, a fluorescence light source 10 and a fluorescence camera 11, wherein the fluorescence light source 10 irradiates an image of a sample 21, transmits through the dichroic mirror 3 of the conversion cube 4, is filtered by the light filter 9, and is photographed by the fluorescence camera 11, and the dichroic mirror 3, the light filter 9 and the fluorescence light source 10 can be replaced according to a specific imaging label probe.

The optical imaging system of the four-mode photoacoustic, ultrasonic, fluorescence and optical imaging microscope further comprises an optical shooting camera 12, an ocular 13, an optical reflector 14, an optical reflector bracket 15, an optical reflector slide rail 16, an optical reflector bracket clamping position 17, a white light source 18 and a microscope shell 19, the optical shooting camera 12 and the ocular 13 are fixed on the microscope shell 19, the optical reflector 14 is fixed on the optical reflector bracket 15, the optical reflector bracket 15 is fixed on the optical reflector slide rail 16, the up-and-down movement of the optical reflector 14 is controlled, and the optical reflector slide rail 16 is fixed on the microscope shell 19.

The optical imaging system of the four-mode photoacoustic, ultrasonic, fluorescent and optical imaging microscope further comprises a replaceable reflector which is positioned at the position of the dichroic mirror 3, when the optical reflector slide rail 16 moves to the lower end, the dichroic mirror 3 in the conversion cube 4 is changed into a reflector, the image of a total reflection sample enters the eyepiece 13 and the optical shooting camera 12 and is in an optical imaging mode, and when the optical reflector slide rail 16 moves to the upper end, the image enters the photoacoustic, ultrasonic or fluorescent mode.

The utility model provides a light path conversion equipment of four modality optoacoustic, supersound, fluorescence and optical imaging microscope, still includes two-dimentional electronic displacement platform 20, two-dimentional electronic displacement platform 20 is fixed under connecting plate 8, optoacoustic, supersound imaging system pass through two-dimentional electronic displacement platform 20 scanning imaging, fluorescence, optical imaging system pass through fluorescence light source 10 or the direct irradiation sample 21 of white light source 18 and develop images.

In short, the photoacoustic imaging device can realize simultaneous or independent photoacoustic imaging, ultrasonic imaging, fluorescence imaging and optical imaging, the optical imaging light path, the fluorescence imaging light path and the photoacoustic imaging light path are integrated together, the optical imaging mode and the photoacoustic imaging mode are controlled by the up-and-down movement of the optical reflector, the fluorescence imaging mode is realized by the replacement of the dichroic mirror and the optical filter, and simultaneous or separate imaging of the photoacoustic imaging mode and the ultrasonic imaging mode is realized by the control of the background host software system. The quick, flexible and simple switching of four modes is realized.

The above-described embodiments are merely illustrative of the several embodiments of the present invention, and the present invention is not limited to the above-described embodiments, and those skilled in the art can make modifications and variations of the present invention. Any modification, equivalent replacement, improvement and the like made within the spirit and principle of the present application shall be included in the protection scope of the present application.