CN116649910A - Molecular imaging system and detection method - Google Patents
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Abstract
The invention relates to the technical field of cancer cell imaging, in particular to a molecular imaging system which has strong tissue penetrability, can quantitatively analyze images and improves detection precision; comprising the following steps: the system comprises a central control module, a single photon emission computer tomography module and a near infrared fluorescence small animal living body imaging system; the single photon emission computer tomography module and the near infrared fluorescence small animal living body imaging system are used for collecting the influence information of the radionuclide biological carrier; the central control module is used for controlling and processing the image information collected by the single photon emission computer tomography module and the near infrared fluorescence living animal imaging system in a centralized way, and the central control module is connected with the computer terminal through a local area network.
Description
Technical Field
The invention relates to the technical field of cancer cell imaging, in particular to a molecular imaging system and a detection method.
Background
The existing imaging detection system for biological cancer cells mostly uses single-mode molecular images for imaging, such as electron emission tomography, has the advantages of high sensitivity and quantitative analysis, but has poor spatial resolution, and the imaging effect is not ideal, and the other optical imaging has the advantages of high spatial resolution and high sensitivity, but has poor penetration of near infrared light tissue, is only suitable for imaging animals with smaller sizes or superficial organs, and is difficult to convert into clinic.
Disclosure of Invention
In order to solve the technical problems, the invention provides a molecular imaging system which has strong tissue penetrability, can quantitatively analyze images and improves detection accuracy.
The invention relates to a molecular imaging system, which comprises: the system comprises a central control module, a single photon emission computer tomography module and a near infrared fluorescence small animal living body imaging system;
the single photon emission computer tomography module and the near infrared fluorescence small animal living body imaging system are used for collecting the influence information of the radionuclide biological carrier;
the central control module is used for intensively controlling and processing image information acquired by the single photon emission computer tomography module and the near infrared fluorescence small animal living body imaging system, and is connected with the computer terminal through a local area network.
Further, the single photon emission computed tomography module comprises an image processor, a collimator and a detector, wherein the collimator is used for enabling the coupling of the light to enter the image processor in a maximum efficiency mode, the thickness of a probe crystal of the detector is set to be 1mm to 9.5mm, and the image processor is used for receiving image signals and integrating the image signals into an image.
Further, the near infrared fluorescence small animal living body imaging system comprises an image display, a detector and a light source;
the detector also comprises an infrared image sensor and a fluorescent nano probe surface morphology and absorption spectrum detection device, wherein the infrared image sensor is used for receiving a transmission signal of fluorescein in the body of the small animal; wherein the fluorescent nanoprobe is used for being combined with a target object of magnetic nanoparticles, and the magnetic nanoparticles can identify targeted small molecules, polypeptides or antibodies of cancer cells;
the light source adopts two near infrared solid state lasers and an LED white light source, and is used for emitting near infrared light and exciting fluorescein in the body of the small animal to emit a light source for emitting a signal;
the image display is used for converting the fluorescein emission signal in the animal body acquired by the detector into an electric signal, and then outputting the electric signal to the computer for signal processing and image reconstruction, and displaying.
Further, a temperature controller is arranged outside the near infrared fluorescence small animal living body imaging system and is used for regulating and controlling the temperature of the near infrared fluorescence small animal living body imaging system to be 32-42 ℃.
Further, the quantum conversion efficiency of the infrared image sensor is >90%.
In another aspect, a method for detecting a molecular imaging system includes the steps of:
s1: fixing the small animal on the surface of the experiment table;
s2: modifying a targeting small molecule, polypeptide or antibody capable of recognizing cancer cells on the surface of the magnetic nanoparticle;
s3: enriching cancer cells on the surface of the magnetic nano particles obtained in the step S2 through antibodies or nucleic acid aptamer and injecting the cancer cells into a small animal;
s4: combining a fluorescent nano probe capable of specifically recognizing cancer cells with the target of the magnetic nano particles obtained in the step S3;
s5: separating a sandwich structure with an antibody or a nucleic acid aptamer-target-fluorescent nano probe on the surface of the magnetic nano particle;
s6: collecting in-vivo fluorescence signals of the small animals through an infrared image sensor of a near infrared fluorescence living animal imaging system detector, and detecting the morphology and the absorption spectrum of the fluorescent nanoprobe by utilizing a fluorescent nanoprobe surface morphology and absorption spectrum detection device;
s7: and determining the concentration of the cancer cells in the small animal body according to the shape and the absorption spectrum of the fluorescent nano probe.
Further, the magnetic nanoparticles in the step S2 are superparamagnetic iron oxide nanoparticles.
Further, the fluorescent nano probe in the step S3 is nano gold particles.
Compared with the prior art, the invention has the beneficial effects that: the method has the advantages of high spatial resolution, high sensitivity and no ionizing radiation to living organisms, can be used for carrying out nondestructive detection on the living organisms, and improves the detection precision by combining the method with a single photon emission computer tomography module and utilizing the characteristics of strong tissue penetrability and quantitative analysis of images of the single photon emission computer tomography module.
Drawings
FIG. 1 is a schematic diagram of a system architecture of the present invention;
FIG. 2 is a flow chart of the detection method of the present invention.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments.
In the description of the present invention, it should be noted that the directions or positional relationships indicated as being "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc. are directions or positional relationships based on the drawings are merely for convenience of describing the present invention and simplifying the description, and do not indicate or imply that the devices or elements to be referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus should not be construed as limiting the present invention.
In the description of the present invention, it should be noted that, unless explicitly specified and limited otherwise, the terms "mounted," "connected," and "connected" are to be construed broadly, and may be either fixedly connected, detachably connected, or integrally connected, for example; can be mechanically or electrically connected; the connection may be direct or indirect via an intermediate medium, or may be internal communication between two elements. The specific meaning of the above terms in the present invention will be understood in specific cases by those of ordinary skill in the art. This example was written in a progressive manner.
Example 1
As shown in fig. 1 to 2, a molecular imaging system includes a central control module, a single photon emission computed tomography module, and a near infrared fluorescence small animal living body imaging system;
the single photon emission computer tomography module and the near infrared fluorescence small animal living body imaging system are used for collecting the influence information of the radionuclide biological carrier;
the central control module is used for controlling and processing the image information collected by the single photon emission computer tomography module and the near infrared fluorescence living animal imaging system in a centralized way, and the central control module is connected with the computer terminal through a local area network.
Specifically, the single photon emission computed tomography module comprises an image processor, a collimator and a detector; the collimator is used for coupling the light into the image processor in maximum efficiency, the thickness of the probe crystal of the detector is set to be 1mm to 9.5mm, and the image processor is used for receiving the image signals and integrating the image signals into an image; through the arrangement, the image processor, the collimator and the detector can effectively couple light into the image processor at maximum efficiency, and integrate received image signals into images, so that the imaging resolution and the signal-to-noise ratio of the system can be improved, and clearer and more accurate molecular image images can be obtained; the thickness of the probe crystal of the detector is set to be 1mm to 9.5mm, so that different experimental requirements can be met by selecting crystals with different thicknesses, and the detection capability and the spatial resolution of the system can be improved by selecting the proper thickness of the probe crystal.
Specifically, the near infrared fluorescence living animal imaging system comprises an image display, a detector and a light source; the detector also comprises an infrared image sensor and a fluorescent nano probe surface morphology and absorption spectrum detection device, and the infrared image sensor is used for receiving the emission signal of the fluorescein in the animal body; the fluorescent nano probe is used for being combined with a target object of magnetic nano particles, and the magnetic nano particles can identify targeted small molecules, polypeptides or antibodies of cancer cells; the light source adopts two near infrared solid state lasers and an LED white light source, and is used for emitting near infrared light and exciting fluorescein in the body of the small animal to emit a light source for emitting a signal; the image display is used for converting the fluorescein emission signal in the animal body acquired by the detector into an electric signal, and outputting the electric signal to the computer for signal processing and image reconstruction, and displaying;
in the near infrared fluorescence living animal imaging system, the detector adopts an infrared image sensor and a fluorescence nanometer probe surface morphology and absorption spectrum detection device, can accurately collect the emission signal of the fluorescein in the living animal body, and detect the surface morphology and absorption spectrum of the fluorescence nanometer probe, thereby further improving the imaging quality and precision. Meanwhile, the light source adopts two near infrared solid state lasers and one LED white light source, can emit near infrared light, and excites the luciferin in the animal body to emit a light source emitting a signal, thereby being beneficial to improving the detection sensitivity of the system to the luciferin.
In this embodiment, the near infrared fluorescence living animal imaging system has high sensitivity, and can detect fluorescence signals, and the sensitivity can be further improved by the types of the nanoparticles and the performance of the fluorescent probe; the near infrared fluorescence living body imaging system of the small animals has higher spatial resolution, and can detect a very small cancer range area; the molecular imaging system uses a near infrared fluorescence living body imaging technology of the small animals, can directly detect cancer cells in the small animals without excision or puncture, and is a non-invasive technology; compared with the traditional detection method, the near infrared fluorescence small animal living body imaging technology of the molecular imaging system is high in speed, detection can be completed in a short time, and detection time is shortened; near infrared fluorescent small animal living imaging technology of a molecular imaging system can provide high-resolution pixel data.
In conclusion, the near infrared fluorescence living animal imaging system has the advantages of high spatial resolution, high sensitivity, no ionizing radiation to living organisms and the like, can be used for carrying out nondestructive detection on the living organisms, but due to the fact that the near infrared light tissue penetrability adopted by the near infrared fluorescence living animal imaging system is poor, the tissue penetrability of the single photon emission computer tomography module is high and the characteristics of quantitatively analyzing images are utilized by combining with the single photon emission computer tomography module, bimodal imaging can be realized, and the detection precision is improved; the central control module can intensively control and process the image information acquired by the single photon emission computer tomography module and the near infrared fluorescence small animal living body imaging system, thereby being beneficial to improving the overall reliability and the working efficiency of the system.
In the molecular imaging system, an external temperature controller is also arranged for regulating and controlling the temperature of the near infrared fluorescence living animal imaging system to be 32-42 ℃. In the embodiment, the sensitivity degree of the living tissue of the small animal to different temperatures is different, so that the quality and the precision of imaging can be ensured on the premise of controlling the temperature; if the temperature is too high or too low, it may cause damage or injury to the tissue, which may affect effective imaging. Therefore, the controlled temperature can reduce tissue damage, enhance the stability of system imaging and ensure the reliability of results; the controller can be widely applied to different types of animals including mice, rats and the like, and can be used for research based on molecular imaging in the bodies of small animals.
Example two
The method for detecting the cancer cells in the U87MG human brain glioma nude mice by using the molecular imaging system comprises the following steps:
s1: fixing a U87MG human brain glioma nude mouse on the surface of an experiment table, and ensuring the stability of the nude mouse in the detection process;
s2: the magnetic nano-particles are modified with targeting small molecules, polypeptides or antibodies capable of recognizing cancer cells, so that the specific detection of the cancer cells can be realized;
s3: enriching cancer cells on the surface of the magnetic nano particles obtained in the step S2 through an antibody or a nucleic acid aptamer, and injecting the cancer cells into a U87MG human brain glioma nude mouse;
s4: combining a fluorescent nano probe capable of specifically recognizing cancer cells with the target object of the magnetic nano particles obtained in the step S3, so that the positions of the cancer cells can be marked;
s5: the sandwich structure with the antibody or the nucleic acid aptamer-target-fluorescent nano probe on the surface of the magnetic nano particle is separated, so that the influence of stray light on an imaging result can be eliminated;
s6: collecting in-vivo fluorescence signals of the small animals through an infrared image sensor of a near infrared fluorescence living body imaging system detector, and detecting the morphology and the absorption spectrum of the fluorescent nano probe by utilizing a fluorescent nano probe surface morphology and absorption spectrum detection device, so that the positions and the number of cancer cells in the U87MG human brain glioma nude mice can be obtained;
s7: according to the appearance and the absorption spectrum of the fluorescent nano probe, determining the concentration of cancer cells in the U87MG human brain glioma nude mice, and further analyzing the detection result.
Specifically, the magnetic nanoparticles in S2 are superparamagnetic iron oxide nanoparticles, and the superparamagnetic iron oxide nanoparticles are mainly distributed in tissues and organs rich in reticuloendothelial cells, such as liver, spleen, lymph node, bone marrow and the like, so that the contrast ratio of magnetic resonance imaging of tumors and normal tissues at the above parts is improved, and meanwhile, the magnetic nanoparticles have strong clinical transformation potential due to the characteristics of high efficiency, safety and the like, and can be used for detecting various tumors and other diseases.
The fluorescent nano probe in S4 is nano gold particles, and the nano gold particles have the characteristics of controllable form and size, mild surface chemical property, good biocompatibility and the like, and compared with the traditional CT contrast agent, the nano gold particles have the following advantages: higher atomic number, electron density and X-ray absorption coefficient can theoretically provide more superior CT contrast performance; no cytotoxicity; the surface is easily modified by targeting proteins, specific biomarkers and the like, so that a series of molecular probes which can be developed by different imaging devices are designed; normal humans or animals contain little distal elements, and prions are easily quantified and characterized by the commonly used elemental analysis method of inductively coupled plasma mass spectrometry, thereby better validating with imaging results.
The detection method can realize noninvasive detection of the cancer cells in the bodies of the small animals, and has high accuracy and repeatability. The method has the advantages that: specific detection of cancer cells can be achieved by using specialized magnetic nanoparticles and fluorescent nanoprobes; the near infrared fluorescence living animal imaging system is used for imaging, so that the accuracy and precision of detection can be improved, and extra injury or discomfort to the animal can be avoided; in addition, in the detection process, the temperature of the small animal can be regulated to be kept in a proper range, so that the detection accuracy and repeatability are further improved.
The molecular imaging system and the detection method of the invention have common mechanical modes in the installation mode, the connection mode or the setting mode, and can be implemented as long as the beneficial effects can be achieved.
The foregoing is merely a preferred embodiment of the present invention, and it should be noted that it will be apparent to those skilled in the art that modifications and variations can be made without departing from the technical principles of the present invention, and these modifications and variations should also be regarded as the scope of the invention.
Claims (8)
1. A molecular imaging system, comprising: the system comprises a central control module, a single photon emission computer tomography module and a near infrared fluorescence small animal living body imaging system;
the single photon emission computer tomography module and the near infrared fluorescence small animal living body imaging system are used for collecting the influence information of the radionuclide biological carrier;
the central control module is used for intensively controlling and processing image information acquired by the single photon emission computer tomography module and the near infrared fluorescence small animal living body imaging system, and is connected with the computer terminal through a local area network.
2. A molecular imaging system according to claim 1, wherein the single photon emission computed tomography module comprises an image processor, a collimator for maximum efficient coupling of light into the image processor, and a detector having a probe crystal thickness set between 1mm and 9.5mm, the image processor for receiving image signals and integrating into an image.
3. The molecular imaging system of claim 2, wherein the near infrared fluorescent in vivo imaging system comprises an image display, a detector, and a light source;
the detector also comprises an infrared image sensor and a fluorescent nano probe surface morphology and absorption spectrum detection device, wherein the infrared image sensor is used for receiving a transmission signal of fluorescein in the body of the small animal; wherein the fluorescent nanoprobe is used for being combined with a target object of magnetic nanoparticles, and the magnetic nanoparticles can identify targeted small molecules, polypeptides or antibodies of cancer cells;
the light source adopts two near infrared solid state lasers and an LED white light source, and is used for emitting near infrared light and exciting fluorescein in the body of the small animal to emit a light source for emitting a signal;
the image display is used for converting the fluorescein emission signal in the animal body acquired by the detector into an electric signal, and then outputting the electric signal to the computer for signal processing and image reconstruction, and displaying.
4. A molecular imaging system according to claim 3, wherein a temperature controller is arranged outside the near infrared fluorescence live small animal imaging system, and the temperature controller is used for controlling the temperature of the near infrared fluorescence live small animal imaging system to be 32-42 ℃.
5. A molecular imaging system according to claim 3, wherein the quantum conversion efficiency of the infrared image sensor is >90%.
6. A method of molecular imaging system according to claim 3, comprising the steps of:
s1: fixing the small animal on the surface of the experiment table;
s2: modifying a targeting small molecule, polypeptide or antibody capable of recognizing cancer cells on the surface of the magnetic nanoparticle;
s3: enriching cancer cells on the surface of the magnetic nano particles obtained in the step S2 through antibodies or nucleic acid aptamer and injecting the cancer cells into a small animal;
s4: combining a fluorescent nano probe capable of specifically recognizing cancer cells with the target of the magnetic nano particles obtained in the step S3;
s5: separating a sandwich structure with an antibody or a nucleic acid aptamer-target-fluorescent nano probe on the surface of the magnetic nano particle;
s6: collecting in-vivo fluorescence signals of the small animals through an infrared image sensor of a near infrared fluorescence living animal imaging system detector, and detecting the morphology and the absorption spectrum of the fluorescent nanoprobe by utilizing a fluorescent nanoprobe surface morphology and absorption spectrum detection device;
s7: and determining the concentration of the cancer cells in the small animal body according to the shape and the absorption spectrum of the fluorescent nano probe.
7. The method of claim 6, wherein the magnetic nanoparticles in S2 are superparamagnetic iron oxide nanoparticles.
8. The method of claim 6, wherein the fluorescent nanoprobe in S3 is a nanoparticle.
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