CN111938685A - A gamma-fluorescence dual-mode imaging device and imaging method - Google Patents

Abstract

The invention provides a gamma-fluorescence dual-mode imaging device and an imaging method, wherein the method comprises the following steps: injecting a tracer and a fluorescent imaging probe to the object to be detected and performing anesthesia operation; the imaging equipment starts to work, and the gamma imaging acquisition module and the fluorescence imaging acquisition module respectively collect projection information at different angles; after the two parts of projection information images are reconstructed, rigid registration and image fusion are carried out on the two image slices. The gamma-fluorescence dual-mode imaging device and the imaging method fully play the advantages of PET and fluorescence imaging technology combination, and the images after registration and fusion contain imaging information of nuclide contrast and optical contrast, so that the tumor can be more accurately positioned, and the gamma-fluorescence dual-mode imaging device and the imaging method have the characteristics of multiple information content, low respiration artifact, high imaging speed, high depth resolution and the like.

Description

Translated fromChinese

一种伽马-荧光双模成像设备及成像方法A gamma-fluorescence dual-mode imaging device and imaging method

技术领域technical field

本发明涉及医学影像领域，尤其涉及一种伽马-荧光双模成像设备及成像方法。The invention relates to the field of medical imaging, in particular to a gamma-fluorescence dual-mode imaging device and an imaging method.

背景技术Background technique

正电子发射断层(Positron Emission Tomography，简称PET)是一种非侵入性的新型医学技术，能无创、定量、动态地评估动物或者人体活体内各种器官和组织的代谢水平、生化反应和功能活动。相较于X射线计算机断层成像(Computed Tomography，简称CT)和磁共振(Magnetic Resonance Imaging，简称MRI)等结构成像工具，PET的功能成像特性对于生化反应异常敏感(灵敏度为，通常使用对生化反应可检测浓度的极限值作为影像设备灵敏度的评价指标)，可以在疾病发生解剖学变异之前进行检测。Positron Emission Tomography (PET) is a non-invasive new medical technology that can non-invasively, quantitatively and dynamically assess the metabolic levels, biochemical reactions and functional activities of various organs and tissues in animals or humans. . Compared with structural imaging tools such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI), the functional imaging properties of PET are very sensitive to biochemical reactions (the sensitivity is usually The limit of detectable concentration is used as an evaluation index of the sensitivity of imaging equipment), which can be detected before the anatomical variation of the disease occurs.

PET成像属于核素显像的一种，其原理都是基于所谓的示踪原则(TracerPrinciple)：选择一种具有生物活性的放射性示踪剂，其被注射入活体后不会干扰活体的功能并且将参与活体的正常生理活动，因此示踪剂在活体内的时空分布反映了活体的某种特定生理功能和代谢情况。放射性示踪剂中的放射性核素衰变后释放射线或者正电子(随后湮灭产生伽马射线)，仪器探测到这些射线并通过算法推断出放射性示踪剂的时空分布，从而分析活体的生理功能和代谢情况。PET imaging is a type of radionuclide imaging, and its principles are based on the so-called Tracer Principle: a biologically active radiotracer is selected that will not interfere with the function of the living body after being injected into the living body. It will participate in the normal physiological activities of the living body, so the temporal and spatial distribution of the tracer in the living body reflects a specific physiological function and metabolic situation of the living body. The radionuclide in the radioactive tracer decays and releases rays or positrons (subsequent annihilation to produce gamma rays), the instrument detects these rays and infers the spatiotemporal distribution of the radioactive tracer through algorithms, thereby analyzing the physiological function and metabolism.

荧光分子断层成像(nuorescence molecular tom.ography，简称FMT)属于光学分子断层成像的一种，它使用具有特异性的荧光分子探针标记特定的分子或细胞使之作为成像源，用外源光激发生物体内荧光团分子发出波长较激发光更长的荧光，通过检测该荧光来重建出荧光团在生物体内的分布，以实现在体观测细胞或分子水平的变化。早期的荧光断层成像研究重点在于对强散射媒质中的荧光产额和荧光寿命进行直接重建，因为它们可以反映肿瘤内部的代谢和环境状况，对疾病诊疗具有重要意义。Fluorescence molecular tomography (FMT for short) is a type of optical molecular tomography, which uses specific fluorescent molecular probes to label specific molecules or cells as imaging sources and excite them with external light. The fluorophore molecules in the organism emit fluorescence with a longer wavelength than the excitation light, and the distribution of the fluorophore in the organism can be reconstructed by detecting the fluorescence, so as to observe the changes at the cellular or molecular level in vivo. Early fluorescence tomography studies focused on the direct reconstruction of fluorescence yields and fluorescence lifetimes in strongly scattering media, because they can reflect the metabolic and environmental conditions inside tumors and are of great significance for disease diagnosis and treatment.

FMT系统不仅为在体分子成像提供了平台，还能够促进基于分子成像的实验研究。但FMT系统得到的图像反映的信息有限，无法从中获得如解剖学结构等其他层面上的信息，因此会对病灶的定位及对药物的运输和摄取的监控带来困难；另一方面FMT系统数据的重建过程影响着成像性能的优劣，正向模型的不准确和逆向问题的病态性限制了FMT的重建性能。FMT systems not only provide a platform for in vivo molecular imaging, but also facilitate molecular imaging-based experimental studies. However, the information reflected by the images obtained by the FMT system is limited, and other levels of information such as anatomical structures cannot be obtained from it, so it will bring difficulties to the localization of the lesions and the monitoring of the transportation and intake of drugs; on the other hand, the FMT system data The reconstruction process of FMT affects the imaging performance, and the inaccuracy of the forward model and the ill-posedness of the inverse problem limit the reconstruction performance of FMT.

将荧光成像技术与正电子发射断层成像结合在一起，用于肿瘤外科手术和微小肿瘤检测，更好地解决肿瘤外科手术问题，提高成像的深度分辨力。其中正电子发射断层成像，作为核医学领域最先进的临床检查影像技术，可提供病灶区域详尽的功能与代谢等分子信息，具有灵敏、准确、特异及定位精确等特点。与荧光成像相比，PET成像探测到的高能伽马射线可以顺利穿透人体深部组织，受组织深度影响小，对深处肿瘤的定位、探测具有很大的优势。The combination of fluorescence imaging technology and positron emission tomography imaging is used for tumor surgery and small tumor detection to better solve the problem of tumor surgery and improve the depth resolution of imaging. Among them, positron emission tomography, as the most advanced clinical examination imaging technology in the field of nuclear medicine, can provide detailed molecular information such as function and metabolism in the lesion area, and has the characteristics of sensitivity, accuracy, specificity and precise positioning. Compared with fluorescence imaging, the high-energy gamma rays detected by PET imaging can smoothly penetrate deep tissues of the human body, and are less affected by the depth of tissues, and have great advantages in the localization and detection of deep tumors.

通过伽马-荧光双模成像可充分发挥PET、荧光成像技术结合的优势，可以针对肿瘤部位进行精确定位，PET成像探测深度深，正电子核素对肿瘤组织的靶向性好，术中检测灵敏度高，荧光成像具有微小病灶分辨率高，灵敏度好，高精度定位等优点。伽马-荧光双模融合成像设备具有优势互补，伽马成像提供基于核素对比的功能成像信息，荧光成像提供基于光学对比的成像信息，两者融合后的图像可同时反映以上双重信息，同时便于两种模态数据的比较和验证。Gamma-fluorescence dual-mode imaging can give full play to the advantages of the combination of PET and fluorescence imaging technology, and can accurately locate the tumor site. High sensitivity, fluorescence imaging has the advantages of high resolution of small lesions, good sensitivity, and high-precision positioning. Gamma-fluorescence dual-mode fusion imaging equipment has complementary advantages. Gamma imaging provides functional imaging information based on nuclide contrast, and fluorescence imaging provides imaging information based on optical contrast. The image after fusion can reflect the above dual information at the same time. It is convenient to compare and verify the two modal data.

发明内容SUMMARY OF THE INVENTION

本发明的目的是提供一种伽马-荧光双模成像设备及成像方法，通过伽马-荧光双模融合成像设备优势互补，对重建后的两图像配准、融合，对肿瘤进行更加精确定位。The purpose of the present invention is to provide a gamma-fluorescence dual-mode imaging device and an imaging method, through the complementary advantages of the gamma-fluorescence dual-mode fusion imaging device, the two reconstructed images are registered and fused, and the tumor can be located more accurately .

为了解决上述技术问题，提供了一种伽马-荧光双模成像设备，包括伽马图像采集模块、荧光成像采集模块、图像重建模块、配准融合模块、显示模块；In order to solve the above technical problems, a gamma-fluorescence dual-mode imaging device is provided, including a gamma image acquisition module, a fluorescence imaging acquisition module, an image reconstruction module, a registration fusion module, and a display module;

所述伽马成像采集模块，与图像重建模块连接，用于传输伽马成像的投影信息，伽马成像采集模块包括闪烁晶体模块、SiPM模块、电子学模块；The gamma imaging acquisition module is connected to the image reconstruction module for transmitting projection information of gamma imaging, and the gamma imaging acquisition module includes a scintillation crystal module, a SiPM module, and an electronics module;

所述电子学模块，用于对闪烁脉冲信号进行处理，包括放大器模块、模拟集成电路模块、高速ADC模块、符合电路模块；The electronics module is used to process the scintillation pulse signal, including an amplifier module, an analog integrated circuit module, a high-speed ADC module, and a conforming circuit module;

所述荧光成像采集模块与图像重建模块连接，用于传输荧光成像的投影数据，荧光成像采集模块包括激光模块、激光传输模块、待测物模块、荧光收集模块；The fluorescence imaging acquisition module is connected to the image reconstruction module, and is used for transmitting the projection data of fluorescence imaging, and the fluorescence imaging acquisition module includes a laser module, a laser transmission module, a test object module, and a fluorescence collection module;

所述激光传输模块，用于将所需波长的光线导向样品，从而保证激发光的单一性，激光传输模块包括折射镜模块、聚焦透镜模块；The laser transmission module is used to guide the light of the required wavelength to the sample, so as to ensure the unity of the excitation light, and the laser transmission module includes a refractor module and a focusing lens module;

所述荧光收集模块，用于负责拟合不同波长的发射光、保证线性关系和透过性，最后采集荧光投影数据，荧光收集模块包括二向色滤光器模块、发射滤镜模块、信号检测放大模块、CCD模块；The fluorescence collection module is responsible for fitting the emitted light of different wavelengths, ensuring linear relationship and permeability, and finally collecting fluorescence projection data. The fluorescence collection module includes a dichroic filter module, an emission filter module, and a signal detection module. Amplification module, CCD module;

所述图像重建模块与伽马成像采集模块、荧光成像采集模块和配准融合模块连接，用于接收荧光投影信息和伽马投影信息，并分别对两种投影信息采用相关算法进行图像重建；The image reconstruction module is connected with the gamma imaging acquisition module, the fluorescence imaging acquisition module and the registration and fusion module, and is used for receiving the fluorescence projection information and the gamma projection information, and respectively using the correlation algorithm to reconstruct the image for the two projection information;

所述配准融合模块与图像重建模块和显示模块连接，用于将伽马3D成像与荧光3D成像进行刚性配准后对两图进行融合；The registration and fusion module is connected with the image reconstruction module and the display module, and is used to fuse the two images after performing rigid registration of the gamma 3D imaging and the fluorescence 3D imaging;

所述显示模块，与配准融合模块连接，用于将融合后的图像进行显示。The display module is connected with the registration and fusion module, and is used for displaying the fused image.

一种伽马-荧光双模成像方法，所述方法包括以下步骤：A gamma-fluorescence dual-mode imaging method, comprising the following steps:

步骤S1：对待测小动物注射示踪剂及麻醉后，将小动物固定在待测物模块的旋转盘中，推至待测物模块探测器中心处，激光模块光源对准待测小动物；Step S1: after the small animal to be tested is injected with tracer and anesthetized, the small animal is fixed in the rotating disc of the object to be tested module, pushed to the center of the detector of the object to be tested module, and the light source of the laser module is aimed at the small animal to be tested;

步骤S2：整个系统开始工作，激光经过传输，照射在待测小动物上产生荧光信号，经过收集与检测放大由CCD采集荧光投影数据；Step S2: the whole system starts to work, the laser is transmitted and irradiated on the small animal to be tested to generate a fluorescent signal, and the fluorescent projection data is collected by the CCD after collection and detection and amplification;

步骤S3：待测小动物体内发出的伽马光子被闪烁晶体接收，经过SiPM模块光电转换及电子学前端处理后伽马投影数据传输至图像重建模块；Step S3: The gamma photons emitted by the small animal to be tested are received by the scintillation crystal, and the gamma projection data is transmitted to the image reconstruction module after photoelectric conversion by the SiPM module and electronic front-end processing;

步骤S4：在图像重建模块中分别对伽马与荧光成像，最后对两图像切片进行相应的刚性配准后，将两图像进行融合。Step S4 : respectively image gamma and fluorescence in the image reconstruction module, and finally fuse the two images after performing corresponding rigid registration on the slices of the two images.

优选的，高速ADC为采样率40MSPS、采样精度12Bits的模数转换器。Preferably, the high-speed ADC is an analog-to-digital converter with a sampling rate of 40 MSPS and a sampling accuracy of 12 Bits.

优选的，探测器为结构较简单的双平板PET探测器。Preferably, the detector is a double-plate PET detector with a relatively simple structure.

优选的，SiPM模块采用的SiPM阵列基本微元数大于3000。Preferably, the SiPM array used by the SiPM module has more than 3000 basic elements.

优选的，激光模块使用激发光带宽大于60nm相对较宽的LED光源。Preferably, the laser module uses an LED light source with a relatively wide excitation light bandwidth greater than 60 nm.

优选的，伽马成像的重建算法为3D-OSEM算法，荧光成像的重建算法为ART算法。Preferably, the reconstruction algorithm of gamma imaging is 3D-OSEM algorithm, and the reconstruction algorithm of fluorescence imaging is ART algorithm.

优选的，对伽马和荧光投影信息采用动态采样的模式。Preferably, a dynamic sampling mode is used for the gamma and fluorescence projection information.

优选的，在检测前对待测小动物采用麻醉蒸发器进行麻醉。Preferably, the small animal to be tested is anesthetized with an anesthesia vaporizer before detection.

优选的，待测物模块中间为受系统控制的旋转盘，系统工作时旋转盘匀速旋转360°，待测物模块旋转盘内装有固定待测小动物的固定夹。Preferably, in the middle of the object to be tested module is a rotating disk controlled by the system, the rotating disk rotates 360° at a constant speed when the system is working, and the rotating disk of the object to be tested module is equipped with a fixing clip for fixing the small animal to be tested.

有益效果：Beneficial effects:

本发明一种伽马-荧光双模成像设备及成像方法，充分发挥PET、荧光成像技术结合的优势，配准融合后的图像既含有核素对比的功能成像信息又含有光学对比的成像信息，能够更加精确的对肿瘤进行定位，具有多信息量、呼吸伪影低、成像速度快及深度分辨率高等特点The invention provides a gamma-fluorescence dual-mode imaging device and an imaging method, which fully utilizes the advantages of combining PET and fluorescence imaging technologies, and the image after registration and fusion contains both functional imaging information of radionuclide contrast and imaging information of optical contrast. It can locate tumors more accurately, and has the characteristics of multi-information, low respiratory artifact, fast imaging speed and high depth resolution

附图说明Description of drawings

图1为本发明系统结构框图；Fig. 1 is the system structure block diagram of the present invention;

图2为本发明的荧光成像采集结构示意图；2 is a schematic diagram of the fluorescence imaging acquisition structure of the present invention;

图3为本发明的伽马成像采集结构示意图；3 is a schematic diagram of the gamma imaging acquisition structure of the present invention;

图4为本发明伽马重建的横截面图4 is a cross-sectional view of the gamma reconstruction of the present invention

100、伽马成像模块；110、闪烁晶体模块；120、SiPM模块；130电子学模块；131放大器模块；132模拟集成电路模块；133高速ADC模块；134符合电路模块；200荧光成像模块；210激发模块；220、激光传输模块；221、折射镜模块；222、聚焦透镜模块；230、待测物模块；240、荧光收集模块；241、二向色滤光器模块；242、发射滤镜模块；243、信号检测放大模块；244、CCD模块；300、图像重建模块；400、配准融合模块；500、显示模块。100, gamma imaging module; 110, scintillation crystal module; 120, SiPM module; 130 electronics module; 131 amplifier module; 132 analog integrated circuit module; 133 high speed ADC module; 134 coincidence circuit module; 200 fluorescence imaging module; 210 excitation module; 220, laser transmission module; 221, refractor module; 222, focusing lens module; 230, object to be tested module; 240, fluorescence collection module; 241, dichroic filter module; 242, emission filter module; 243, a signal detection and amplification module; 244, a CCD module; 300, an image reconstruction module; 400, a registration and fusion module; 500, a display module.

具体实施方式Detailed ways

以下结合附图对本发明做进一步详细说明。The present invention will be further described in detail below with reference to the accompanying drawings.

本发明提供一种伽马-荧光双模成像设备及成像方法，包以下模块：伽马图像采集模块100、荧光成像采集模块200、图像重建模块300、配准融合模块400、显示模块500。The present invention provides a gamma-fluorescence dual-mode imaging device and an imaging method, comprising the following modules: a gamma image acquisition module 100 , a fluorescence imaging acquisition module 200 , an image reconstruction module 300 , a registration and fusion module 400 , and a display module 500 .

所述伽马成像采集模块100，与图像重建模块300连接，用于传输伽马成像的投影信息；伽马成像采集模块100包括闪烁晶体模块110、SiPM模块120、电子学模块130；The gamma imaging acquisition module 100 is connected to the image reconstruction module 300 for transmitting projection information of gamma imaging; the gamma imaging acquisition module 100 includes ascintillation crystal module 110, aSiPM module 120, and an electronics module 130;

闪烁晶体模块110，隶属于伽马成像采集模块100，用于吸收伽马射线射入晶体内的伽马光子。Thescintillation crystal module 110 belongs to the gamma imaging acquisition module 100 and is used for absorbing gamma photons injected by gamma rays into the crystal.

SiPM模块120，隶属于伽马成像采集模块100，用于将接收晶体的光信号转化为电脉冲信号。TheSiPM module 120, which belongs to the gamma imaging acquisition module 100, is used to convert the optical signal of the receiving crystal into an electrical pulse signal.

电子学模块130，隶属于伽马成像采集模块100，用于对闪烁脉冲信号进行处理，提取相应信息，包括放大器模块131、模拟集成电路模块132、高速ADC模块133、符合电路模块134。The electronics module 130 , which belongs to the gamma imaging acquisition module 100 , is used to process the scintillation pulse signal and extract corresponding information, including anamplifier module 131 , an analogintegrated circuit module 132 , a high-speed ADC module 133 , and acoincidence circuit module 134 .

放大器模块131，隶属于电子学模块130，用于将电脉冲信号进行放大，减小电容，最大化信噪比。Theamplifier module 131, which belongs to the electronics module 130, is used to amplify the electrical pulse signal, reduce the capacitance, and maximize the signal-to-noise ratio.

模拟集成电路模块132，隶属于电子学器模块130，用于提取电脉冲信号中伽马光子的能量信息、时间信息和位置信息。The analog integratedcircuit module 132, which belongs to the electronics module 130, is used to extract the energy information, time information and position information of the gamma photons in the electrical pulse signal.

高速ADC模块133，隶属于电子学模块130，用于将提取的信息进行数字化处理。The high-speed ADC module 133, which is subordinate to the electronics module 130, is used for digitizing the extracted information.

符合电路模块134，隶属于电子学模块130，用于对伽马光子的能量、时间、位置信息分别做符合处理。Thecoincidence circuit module 134, which belongs to the electronics module 130, is used to respectively perform coincidence processing on the energy, time and position information of the gamma photon.

所述荧光成像采集模块200，与图像重建模块300连接，用于传输荧光成像的投影数据；荧光成像采集模块200包括激光模块210、激光传输模块220、待测物模块230、荧光收集模块240；The fluorescence imaging acquisition module 200 is connected to the image reconstruction module 300 for transmitting projection data of fluorescence imaging; the fluorescence imaging acquisition module 200 includes alaser module 210, a laser transmission module 220, atest object module 230, and a fluorescence collection module 240;

激光模块210，隶属于荧光成像采集模块200，用于发射光源照射待检测样品。Thelaser module 210 belongs to the fluorescence imaging acquisition module 200 and is used for emitting a light source to illuminate the sample to be detected.

激光传输模块220，隶属于荧光成像采集模块200，用于将所需波长的光线导向样品，从而保证激发光的单一性，包括折射镜模块221、聚焦透镜模块222。The laser transmission module 220 , which belongs to the fluorescence imaging acquisition module 200 , is used to guide the light of the required wavelength to the sample, so as to ensure the unity of the excitation light, and includes arefractor module 221 and a focusinglens module 222 .

折射镜模块221，隶属于激光传输模块220，用于改变光源的方向。Therefractor module 221, which is subordinate to the laser transmission module 220, is used to change the direction of the light source.

聚焦透镜模块222，隶属于激光传输模块220，用于控制表面的曲率，利用产生的光程差使光线汇聚成一点。The focusinglens module 222, which is subordinate to the laser transmission module 220, is used to control the curvature of the surface, and use the generated optical path difference to make the light converge to a point.

待测物模块230，隶属于荧光成像采集模块200，用于放置待测物，开始探测时，系统控制待测物随中间圆盘旋转。The object to be testedmodule 230 belongs to the fluorescence imaging acquisition module 200 and is used for placing the object to be tested. When the detection starts, the system controls the object to be tested to rotate with the middle disc.

荧光收集模块240，隶属于荧光成像采集模块200，用于负责拟合不同波长的发射光、保证线性关系和透过性，最后采集荧光投影数据，包括二向色滤光器模块241、发射滤镜模块242、信号检测放大模块243、CCD模块244。The fluorescence collection module 240, which belongs to the fluorescence imaging collection module 200, is responsible for fitting the emitted light of different wavelengths, ensuring the linear relationship and permeability, and finally collecting the fluorescence projection data, including thedichroic filter module 241, the emission filterA mirror module 242 , a signal detection and amplification module 243 , and a CCD module 244 .

二向色滤光器模块241，隶属于荧光收集模块240，用于将不同波长的荧光信号进行分离和折射。Thedichroic filter module 241 is subordinate to the fluorescence collection module 240, and is used to separate and refract fluorescence signals of different wavelengths.

发射滤镜模块242，隶属于荧光收集模块240，用于收集和过滤杂信号。Theemission filter module 242, which is subordinate to the fluorescence collection module 240, is used to collect and filter spurious signals.

信号检测放大模块243，隶属于荧光收集模块240，用于对荧光光能信号放大、转化成电信号。The signal detection and amplification module 243 belongs to the fluorescence collection module 240 and is used for amplifying and converting the fluorescence light energy signal into an electrical signal.

CCD模块244，隶属于荧光收集模块240，用于快速获取多个角度的荧光投影信息。The CCD module 244, which is subordinate to the fluorescence collection module 240, is used to quickly acquire fluorescence projection information from multiple angles.

所述图像重建模块300，与伽马成像采集模块100、荧光成像采集模块200和配准融合模块400连接，用于接收荧光投影信息和伽马投影信息，并分别对两种投影信息采用相关算法进行图像重建。The image reconstruction module 300 is connected to the gamma imaging acquisition module 100, the fluorescence imaging acquisition module 200 and the registration fusion module 400, and is used to receive fluorescence projection information and gamma projection information, and respectively use correlation algorithms for the two projection information Perform image reconstruction.

所述配准融合模块400，与图像重建模块300和显示模块500连接，用于将伽马3D成像与荧光3D成像进行刚性配准后对两图进行融合。The registration and fusion module 400 is connected to the image reconstruction module 300 and the display module 500, and is used to perform rigid registration of the gamma 3D imaging and the fluorescence 3D imaging to fuse the two images.

所述显示模块500，与配准融合模块400连接，用于将融合后的图像进行显示。The display module 500 is connected to the registration and fusion module 400 for displaying the fused image.

实例1：先对具有肿瘤的小老鼠注射示踪剂¹⁸F-FDG，一小时后对小鼠进行麻醉蒸发器麻醉以及对肿瘤部位注射菁绿(ICG)溶液，将待测小老鼠固定在待测物模块230上，并推至伽马成像采集模块100和荧光成像模块200的成像区域中心内。系统开始工作，小老鼠跟随圆盘旋转360°，从获取不同的投影中获取数据。激发模块210发射激发光，经过折射镜模块221折射改变方向，通过聚焦透镜模块222聚焦到小老鼠体内的肿瘤部位上，肿瘤部位荧光团分子发出荧光，荧光在二向色滤光器模块241作用下，不同波长的荧光信号被分离和折射。最后经过发射滤光器模块242滤去杂质信号，由信号检测放大模块将放大分拣后的光信号转化为电信号，随后CCD模块244获取每个角度的荧光投影数据，图像重建模块400通过将每个角度的激发光和荧光图像映射到网格的相应位置中来建立权重矩阵。最后，采用ART的代数重建方法重建3D荧光成像。同时，小鼠体内正电子湮灭产生成对伽马光子，双平板探测器的闪烁晶体模块110吸收小鼠体内发出的伽马光子，并将高能光子转化为可见光，SiPM模块120将产生的光信号转化为电脉冲信号，经过放大器模块131将电脉冲信号进行放大后，模拟集成电路模块132对信号内相应的能量、时间和位置信息进行提取。高速ADC模块133将提取后的模拟信号转化为数字信号，符合电路模块134对各数字信号进行相应的时间窗、能量等符合处理。在获得投影数据后，在图像重建模块300通过3D-OSEM的迭代算法对核素分布图像进行重建。较准融合模块400对伽马与荧光重建的结果在空间中进行刚性配准，并排显示伽马3D成像与荧光3D成像中匹配的切片，并将伽马图像与荧光图像进行融合。最后，再将融合后的图像在显示模块500进行显示，融合后的图像可以将肿瘤的位置与伽马图像区分开，荧光染料在肿瘤的底部显示。Example 1: First, inject the tracer¹⁸ F-FDG into the mice with tumors, and anesthetize the mice with anesthesia vaporizer anesthesia and inject cyanine green (ICG) solution into the tumor site one hour later. The measuringobject module 230 is pushed to the center of the imaging area of the gamma imaging acquisition module 100 and the fluorescence imaging module 200 . The system starts to work, and the mouse follows the disc and rotates 360° to obtain data from different projections. Theexcitation module 210 emits excitation light, which is refracted by therefractor module 221 to change its direction, and focused on the tumor site in the mouse body through the focusinglens module 222. The fluorophore molecules in the tumor site emit fluorescence, and the fluorescence acts on thedichroic filter module 241. , fluorescence signals of different wavelengths are separated and refracted. Finally, the impurity signal is filtered out by theemission filter module 242, and the amplified and sorted optical signal is converted into an electrical signal by the signal detection and amplification module, and then the CCD module 244 obtains the fluorescence projection data of each angle. The excitation light and fluorescence images at each angle are mapped to the corresponding positions on the grid to create a weight matrix. Finally, 3D fluorescence images were reconstructed using the algebraic reconstruction method of ART. At the same time, the positron annihilation in the mouse produces pairs of gamma photons. Thescintillation crystal module 110 of the double flat-panel detector absorbs the gamma photons emitted in the mouse and converts the high-energy photons into visible light. TheSiPM module 120 converts the generated light signal The electrical pulse signal is converted into an electrical pulse signal, and after the electrical pulse signal is amplified by theamplifier module 131, the analog integratedcircuit module 132 extracts the corresponding energy, time and position information in the signal. The high-speed ADC module 133 converts the extracted analog signal into a digital signal, and thecoincidence circuit module 134 performs a corresponding time window, energy and other coincidence processing on each digital signal. After the projection data is obtained, the image reconstruction module 300 reconstructs the nuclide distribution image through the iterative algorithm of 3D-OSEM. The alignment fusion module 400 performs rigid registration of the gamma and fluorescence reconstruction results in space, displays the matched slices in the gamma 3D imaging and the fluorescence 3D imaging side by side, and fuses the gamma image and the fluorescence image. Finally, the fused image is displayed on the display module 500. The fused image can distinguish the position of the tumor from the gamma image, and the fluorescent dye is displayed at the bottom of the tumor.

实例2：在25mm直径的透明玻璃圆柱体填充为1％的脂质内溶液。将直径为3mm的透明玻璃管插入圆柱体中，其中包含0.05mCi¹⁸F-FDG和0.025ml吲哚菁绿(ICG)溶液，用于伽马和荧光成像。通过动态采样模式在待测物模块230中圆盘旋转的同时获取荧光信号和伽马数据。在待测物旋转360度期间，伽马成像模块100总共获取了256个投影，CCD模块260荧光图像的曝光时间为1s，白光图像的时间为0.025s，采集数据后，重建3D荧光图像和3D伽马图像。待测物的实验结果如图3所示为伽马重建的横截面图，其中的放射性示踪剂和荧光染料通过伽马-荧光成像设备重建出来。Example 2: A 25 mm diameter transparent glass cylinder was filled with 1% intralipid solution. A 3 mm diameter transparent glass tube containing 0.05 mCi¹⁸ F-FDG and 0.025 ml indocyanine green (ICG) solution was inserted into the cylinder for gamma and fluorescence imaging. Fluorescence signal and gamma data are acquired while the disk in the object-to-be-tested module 230 rotates in the dynamic sampling mode. During the 360-degree rotation of the object to be tested, the gamma imaging module 100 acquired a total of 256 projections. The exposure time of the CCD module 260 fluorescence image was 1s, and the time of the white light image was 0.025s. After the data was collected, the 3D fluorescence image and 3D image were reconstructed. Gamma image. The experimental result of the test object is shown in Figure 3 as a cross-sectional view of gamma reconstruction, in which the radiotracer and fluorescent dye are reconstructed by a gamma-fluorescence imaging device.

实例3：¹⁸F-FDG是PET对肿瘤检测中最常用的示踪剂，其原理是肿瘤细胞的高代谢特征使得¹⁸F-FDG在肿瘤细胞浓聚，但炎症区域也会由于这种高代谢特性特征使得¹⁸F-FDG发生浓聚现象，所以仅仅使用PET对此类肿瘤检测很可能会出现假阴性的错误判断。一种靶向整合素α_vβ₃受体探针⁹⁹Tc^m-3PRGD2具有更强的肿瘤细胞靶向性，将其与PET探测有机融合，可以在一定程度上大大减少这种错误判断。设计如下实验，通过20gBALB/C裸鼠(16周)进行诱导人肺腺癌A549细胞的皮下注射(2.5x 107.2.5mL)(右肩)和皮下注射促炎物质的杆菌Calmette-Gu注射(Img/ml，分别为0.2mL)，培养具有肿瘤细胞(右肩)以及炎症的小鼠模型。在实验过程中，对小鼠注射¹⁸F-FDG和⁹⁹Tc^m-3PRGD2以及一种近红外荧光染料的荧光成像探针Cy7-entrappedCCPM，麻醉后使用伽马-荧光双模成像设备进行数据采集及图像重建融合。并将实验动物处死后进行组织学切片鉴定。通过将双模态的图像融合，可以准确地确定肿瘤的位置位于右肩上。组织切片也显示了在右肩细胞的高增殖现象。Example 3:¹⁸ F-FDG is the most commonly used tracer in PET for tumor detection. The principle is that the high metabolic characteristics of tumor cells make¹⁸ F-FDG concentrated in tumor cells, but the inflammatory area will also be due to this high metabolism. The characteristic feature makes the¹⁸ F-FDG agglomeration phenomenon, so it is very likely that the detection of such tumors using PET will be false negative. A probe targeting integrin α_v β₃ receptor⁹⁹ Tc^m -3PRGD2 has stronger tumor cell targeting, and organic fusion of it with PET detection can greatly reduce this misjudgment to a certain extent. The following experiments were designed to induce subcutaneous injection (2.5 x 107.2.5 mL) of human lung adenocarcinoma A549 cells through 20 g BALB/C nude mice (16 weeks) (right shoulder) and subcutaneous injection of pro-inflammatory Bacillus Calmette-Gu (1 mg /ml, 0.2 mL, respectively), a mouse model with tumor cells (right shoulder) and inflammation was cultured. During the experiment, mice were injected with¹⁸ F-FDG and⁹⁹ Tc^m -3PRGD2 and a near-infrared fluorescent dye fluorescent imaging probe Cy7-entrappedCCPM. After anesthesia, a gamma-fluorescence dual-mode imaging device was used for data acquisition and analysis. Image reconstruction fusion. The experimental animals were sacrificed for histological section identification. By fusing the bimodal images, it was possible to accurately determine the location of the tumor on the right shoulder. Histological sections also showed high proliferation of cells in the right shoulder.

本发明提供的一种伽马-荧光双模成像设备及成像方法，通过伽马成像提供基于核素对比的功能成像信息，荧光成像提供基于光学对比的成像信息，在刚性配准后对两者图像进行融合，融合后的图像可同时反映以上双重信息，同时便于两种模态数据的比较和交叉验证，对肿瘤部位进行更加精确定位，在小动物检测前使用麻醉蒸发器麻醉及固定夹固定，有效降低了图像的呼吸伪影。小动物在动态采样模式下连续旋转，减少了旋转开始和停止引起的小动物的抖动，提高了成像的速度。整个系统具有多信息量、呼吸伪影低、成像速度快及深度分辨率高等特点。A gamma-fluorescence dual-mode imaging device and imaging method provided by the present invention provide functional imaging information based on nuclide contrast through gamma imaging, and fluorescence imaging provides imaging information based on optical contrast. The images are fused, and the fused image can reflect the above dual information at the same time, which is convenient for the comparison and cross-validation of the two modal data, and more accurately locates the tumor site. Anesthesia vaporizer is used for anesthesia and fixation clips before small animal detection. , effectively reducing the breathing artifacts of the image. The small animal rotates continuously in the dynamic sampling mode, which reduces the shaking of the small animal caused by the start and stop of rotation, and improves the speed of imaging. The whole system has the characteristics of multi-information, low breathing artifacts, fast imaging speed and high depth resolution.

以上所述的，仅为本发明的较佳实施例，并非用以限定本发明的范围，本发明的上述实施例还可以做出各种变化。即凡是依据本发明申请的权利要求书及说明书内容所作的简单、等效变化与修饰，皆落入本发明专利的权利要求保护范围。本发明未详尽描述的均为常规技术内容。The above descriptions are only preferred embodiments of the present invention, and are not intended to limit the scope of the present invention. Various changes can be made to the above-mentioned embodiments of the present invention. That is, all simple and equivalent changes and modifications made according to the claims and descriptions of the present invention fall into the protection scope of the claims of the present invention. What is not described in detail in the present invention is conventional technical content.

Claims (10)

1. A gamma-fluorescence dual mode imaging device, characterized by: the system comprises a gamma image acquisition module, a fluorescence imaging acquisition module, an image reconstruction module, a registration fusion module and a display module;

the gamma imaging acquisition module is connected with the image reconstruction module and is used for transmitting projection information of gamma imaging, and the gamma imaging acquisition module comprises a scintillation crystal module, an SiPM module and an electronics module;

the electronic module is used for processing the scintillation pulse signal and comprises an amplifier module, an analog integrated circuit module, a high-speed ADC module and a coincidence circuit module;

the fluorescence imaging acquisition module is connected with the image reconstruction module and is used for transmitting the projection data of fluorescence imaging, and the fluorescence imaging acquisition module comprises a laser module, a laser transmission module, an object to be detected module and a fluorescence collection module;

the laser transmission module is used for guiding light with required wavelength to the sample so as to ensure the unicity of exciting light, and comprises a refractor module and a focusing lens module;

the fluorescence collection module is used for fitting emitted light with different wavelengths, ensuring linear relation and permeability and finally collecting fluorescence projection data, and comprises a dichroic filter module, an emission filter module, a signal detection amplification module and a CCD (charge coupled device) module;

the image reconstruction module is connected with the gamma imaging acquisition module, the fluorescence imaging acquisition module and the registration fusion module and is used for receiving the fluorescence projection information and the gamma projection information and respectively reconstructing an image of the two projection information by adopting a correlation algorithm;

the registration fusion module is connected with the image reconstruction module and the display module and is used for performing rigid registration on gamma 3D imaging and fluorescence 3D imaging and then fusing the two images;

and the display module is connected with the registration fusion module and is used for displaying the fused image.

2. A method of dual gamma-fluorescence imaging, the method comprising the steps of:

step S1: after injecting tracer and anaesthetizing to the small animal to be detected, fixing the small animal in a rotating disc of the module to be detected, pushing the small animal to the center of a detector of the module to be detected, and aligning a light source of a laser module to the small animal to be detected;

step S2: the whole system starts to work, laser is transmitted to irradiate on the small animal to be detected to generate a fluorescence signal, and fluorescence projection data are collected by the CCD through collection, detection and amplification;

step S3: gamma photons emitted by the small animal body to be detected are received by the scintillation crystal, and gamma projection data are transmitted to the image reconstruction module after photoelectric conversion and electronic front-end processing of the SiPM module;

step S4: and respectively imaging the gamma and the fluorescence in an image reconstruction module, and finally fusing the two images after carrying out corresponding rigid registration on the two image slices.

3. The dual-mode gamma-fluorescence imaging method as claimed in claim 2, wherein the high-speed ADC is an analog-to-digital converter with a sampling rate of 40MSPS and a sampling precision of 12 Bits.

4. A method of dual-mode gamma-fluorescence imaging as claimed in claim 2, wherein the detector is a dual-plate PET detector of relatively simple construction.

5. A method of dual mode gamma-fluorescence imaging as defined in claim 2, wherein the SiPM module employs SiPM arrays having a primitive number greater than 3000.

6. The dual-mode gamma-fluorescence imaging method as claimed in claim 2, wherein the laser module uses a relatively wide LED light source with an excitation bandwidth greater than 60 nm.

7. The dual-mode gamma-fluorescence imaging method as claimed in claim 2, wherein the reconstruction algorithm of gamma imaging is 3D-OSEM algorithm, and the reconstruction algorithm of fluorescence imaging is ART algorithm.

8. A dual gamma-fluorescence imaging method according to claim 2, wherein a dynamic sampling mode is used for the gamma and fluorescence projection information.

9. The gamma-fluorescence dual-mode imaging method of claim 2, wherein the small animal to be tested is anesthetized with an anesthetic vaporizer before detection.

10. The gamma-fluorescence dual-mode imaging method as claimed in claim 2, wherein the rotating disk controlled by the system is arranged in the middle of the object module to be measured, and the rotating disk rotates at a constant speed for 360 degrees when the system works;

and a fixing clamp for fixing the small animal to be detected is arranged in the rotating disc of the object module to be detected.

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