WO2018000186A1 - Fluorescence scattering optical tomography system and method - Google Patents

Fluorescence scattering optical tomography system and method Download PDF

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Publication number
WO2018000186A1
WO2018000186A1 PCT/CN2016/087425 CN2016087425W WO2018000186A1 WO 2018000186 A1 WO2018000186 A1 WO 2018000186A1 CN 2016087425 W CN2016087425 W CN 2016087425W WO 2018000186 A1 WO2018000186 A1 WO 2018000186A1
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laser
sample
imaging
emccd
ray
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PCT/CN2016/087425
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French (fr)
Chinese (zh)
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陈昳丽
付楠
朱艳春
李荣茂
余绍德
陈鸣闽
谢耀钦
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中国科学院深圳先进技术研究院
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Priority to PCT/CN2016/087425 priority Critical patent/WO2018000186A1/en
Publication of WO2018000186A1 publication Critical patent/WO2018000186A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00Apparatus for radiation diagnosis, e.g. combined with radiation therapy equipment
    • A61B6/02Devices for diagnosis sequentially in different planes; Stereoscopic radiation diagnosis
    • A61B6/03Computerised tomographs

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  • the present invention relates to the field of medical imaging technology, and in particular to a fluorescence scattering optical tomography system and method.
  • Fluorescence Diffuse Optical Tomography has the advantages of low cost, easy operation and no radiation. It is commonly used in small animal living imaging.
  • the working principle of FDOT technology is to use laser to scan in a certain plane, implant tumors and corresponding targeted fluorescent reagents in small animals in advance, fluorescent reagents are excited by laser, emit near-infrared light, and obtain excitation light through detectors. Image, through accurate three-dimensional reconstruction to determine the location and distribution of tumors in animals.
  • the existing FDOT technology is difficult to reconstruct, and the depth information is often inaccurate, and the time period for collecting data is long.
  • Embodiments of the present invention provide a fluorescence scattering optical tomography system for obtaining more accurate depth information, reducing reconstruction difficulty, and shortening a data acquisition period.
  • the fluorescence scattering optical tomography system includes:
  • a stage for carrying a sample the sample being implanted with a nano material, the nano material emitting cold light by X-ray irradiation, and emitting fluorescence by laser irradiation;
  • An X-ray source for emitting X-rays to a sample on the stage
  • An X-ray flat panel detector for obtaining CT imaging of the sample by X-ray irradiation
  • EMCCD for obtaining XLCT imaging of the sample by X-ray irradiation
  • the EMCCD is also used to obtain laser-irradiated laser images and fluorescent images of the sample, the laser images, fluorescent images, and CT imaging for reconstructing FDOT imaging.
  • the stage is a rotating stage;
  • the X-ray flat panel detector is specifically configured to obtain CT imaging of a plurality of angles of rotation of the sample on a rotating stage;
  • the EMCCD is specifically used for XLCT imaging of the plurality of angles at which the sample is rotated on the rotating stage is obtained.
  • the fluorescence scattering optical tomography system further comprises:
  • the fluorescence scattering optical tomography system further comprises:
  • a filter disposed between the EMCCD and the stage for filtering the fluorescence emitted by the sample by laser irradiation, so that the EMCCD obtains a laser image of the sample irradiated by the laser; filtering the laser emitted by the laser,
  • the EMCCD was subjected to a laser-irradiated fluorescence image of the sample.
  • Embodiments of the present invention further provide a fluorescence scattering optical tomography method for obtaining more accurate depth information, reducing reconstruction difficulty, and shortening a data acquisition period.
  • the fluorescence scattering optical tomography method includes:
  • Opening an X-ray source and an X-ray flat panel detector the X-ray source emitting X-rays to the sample on the stage, and the X-ray flat panel detector obtains CT imaging of the sample by X-ray irradiation; the EMCCD obtains the sample by X-ray irradiation of XLCT imaging;
  • the EMCCD obtains the laser image and the fluorescent image of the sample irradiated by the laser
  • the laser image, and the fluorescence image, FDOT imaging is reconstructed.
  • the stage is a rotating stage; the sample is rotated on a rotating stage;
  • An X-ray flat panel detector obtains CT imaging of the sample by X-ray irradiation, comprising: an X-ray flat panel detector obtaining CT images of the plurality of angles of rotation of the sample on the rotating stage;
  • the EMCCD obtains X-ray illuminated XLCT imaging of the sample, including: EMCCD obtains multiple angles of XLCT imaging of the sample rotating on a rotating stage.
  • the EMCCD obtains X-ray illuminated XLCT imaging of the sample, including:
  • D(r) is the diffusion coefficient
  • D(r) (3( ⁇ a (r) + (1 - g) ⁇ s (r))) -1
  • ⁇ a (r) is the absorption Coefficient
  • ⁇ s (r) is the scattering coefficient
  • g is the anisotropic parameter
  • ⁇ (r) is the fluorescence intensity
  • S(r) is the light source
  • M is the photon density
  • F is the diffusion coefficient of light divergence
  • is the optical field of view
  • X(r) is the X-ray intensity
  • is the absorption coefficient of light divergence
  • the fluorescence scattering optical tomography method further comprises: the micro-displacement station controls laser movement by clamping a fiber tip of the laser;
  • the EMCCD obtains a laser-irradiated laser image and a fluorescent image of the sample, including: EMCCD obtains a plurality of laser images and fluorescent images of the sample irradiated by the moving laser.
  • the EMCCD obtains laser-irradiated laser images and fluorescent images of the sample, including:
  • a filter is placed between the EMCCD and the stage to filter out the fluorescence emitted by the sample by laser irradiation, and the EMCCD obtains a laser image of the sample irradiated by the laser;
  • the filter is replaced, the laser light emitted by the laser is filtered out, and the EMCCD obtains a fluorescent image of the sample irradiated with laser light.
  • FDOT imaging is reconstructed based on the CT imaging, laser image, and fluorescence image, including:
  • the FDOT imaging is reconstructed based on the body surface information of the sample, the position information of the EMCCD, the sample and the laser, and the laser image and the fluorescence image.
  • the sample is implanted into the nano material, and the nano material emits cold light by X-ray irradiation, and emits fluorescence by laser irradiation; the X-ray source emits X-rays to the sample, and the X-ray flat panel detector obtains the X-ray irradiated sample by the X-ray flat panel detector.
  • EMCCD obtains X-ray XLCT imaging of the sample; laser emits laser light to the sample, EMCCD obtains laser-irradiated laser image and fluorescence image of the sample; laser image, fluorescence image and CT imaging are used to reconstruct FDOT imaging, and FDOT imaging system
  • CT, XLCT and FDOT imaging can be completed in a short time, shortening the data acquisition period, and can make up for the deficiencies of FDOT in depth information, obtain more accurate depth information, and reduce reconstruction difficulty.
  • FIG. 1 is a schematic view of a fluorescence scattering optical tomography system according to an embodiment of the present invention
  • FIG. 2 is a schematic diagram of a CT imaging system exploded by a fluorescence scattering optical tomography system according to an embodiment of the present invention
  • FIG. 3 is a schematic diagram of an XLCT imaging system exploded by a fluorescence scattering optical tomography system according to an embodiment of the present invention
  • FIG. 4 is a schematic diagram of an FDOT imaging system exploded by a fluorescence scattering optical tomography system according to an embodiment of the present invention
  • FIG. 5 is a schematic diagram of a method of fluorescence scattering optical tomography according to an embodiment of the present invention.
  • embodiments of the present invention provide a fluorescence scattering optical tomography system that combines FDOT imaging technology with CT (Computed Tomography).
  • CT Compputed Tomography
  • XLCT X-ray Luminescence Computed Tomography
  • CT imaging is used as a priori information for FDOT imaging data acquisition.
  • the FDOT system is integrated with the CT imaging system, which enables the functional images provided by the FDOT imaging system to be compared and processed by CT imaging, with the aid of CT imaging.
  • the spatial structure is presented more intuitively and accurately.
  • the XLCT imaging system and the FDOT imaging system are spatially fused to obtain accurate prior information and fluorescence information.
  • the fluorescence scattering optical tomography system in the embodiment of the present invention may include:
  • a stage for carrying a sample the sample being implanted with a nano material, the nano material being luminescence by X-ray irradiation, and emitting fluorescence by laser irradiation;
  • An X-ray source for emitting X-rays to a sample on the stage
  • X-ray flat panel detector for obtaining CT image of X-ray irradiation of the sample
  • EMCCD for obtaining XLCT imaging of X-rays of samples
  • the EMCCD is also used to obtain laser-irradiated laser images and fluorescence images of samples, laser images, fluorescence images, and CT imaging for reconstruction of FDOT imaging.
  • the fluorescence scattering optical tomography system of the embodiment of the present invention adopts a method of combining an FDOT imaging system with a CT imaging system and an XLCT imaging system, and completes XLCT, FDOT, and CT in a short time. Imaging, fusion of CT imaging, XLCT imaging and FDOT imaging. As shown in Figure 2-4, The fluorescence scattering optical tomography system can be decomposed into a CT imaging system, an XLCT imaging system, and an FDOT imaging system.
  • the exploded CT imaging system includes an X-ray source and an X-ray flat panel detector.
  • the X-ray is emitted by the X-ray source, the X-ray flat panel detector detects the X-ray signal, and the CT image is reconstructed.
  • FIG. 3 is a schematic diagram of an XLCT imaging system exploded by a fluorescence scattering optical tomography system according to an embodiment of the present invention.
  • the exploded XLCT imaging system includes an X-ray source and an EMCCD (CCD camera). A filter is also included in FIG.
  • the X-ray source emits X-rays to the sample, the nano-materials in the sample are luminescence by X-ray irradiation, and the EMCCD collects luminescence to reconstruct XLCT imaging.
  • XLCT technology is a hot topic in current scientific research, opening up new possibilities for X-ray molecular imaging.
  • nanomaterials can excite near-infrared light under X-rays, and because X-rays and near-infrared light have long penetrability in tissues, they are well suited for imaging in vivo.
  • the tomographic image is obtained from a series of X-ray excitations and is obtained by a highly sensitive CCD (Charge-Coupled Device).
  • CCD Charge-Coupled Device
  • the exploded FDOT imaging system includes a laser and an EMCCD.
  • the laser emits a laser to the sample, and the nanomaterial in the sample is irradiated with laser light to emit fluorescence, and the EMCCD obtains a laser image and a fluorescent image of the collected sample.
  • a collimator that may be included, the laser being a near infrared laser.
  • the stage can be a rotating stage
  • the X-ray flat panel detector can obtain CT imaging of the plurality of angles of the sample rotating on the rotating stage
  • the EMCCD can obtain multiple angles of the sample rotating on the rotating stage.
  • XLCT imaging For example, in the exploded XLCT imaging system shown in Figure 3, the nanomaterial in the sample is excited by the X-ray source to emit luminescence, the sample is rotated on the stage, and the EMCCD obtains luminescence imaging of the sample at various angles.
  • the fluorescence scattering optical tomography system of the embodiment of the present invention may further include: a micro-displacement stage for controlling laser movement by clamping a fiber head of the laser; and the EMCCD is specifically used for obtaining a laser beam irradiated by the sample. Laser images and fluorescent images.
  • the fluorescence scattering optical tomography system of the embodiment of the present invention may further include: a filter disposed between the EMCCD and the stage for filtering the fluorescence emitted by the sample by the laser, so that the EMCCD obtains the sample.
  • a filter disposed between the EMCCD and the stage for filtering the fluorescence emitted by the sample by the laser, so that the EMCCD obtains the sample.
  • Laser-irradiated laser image filtering out the laser from the laser, allowing EMCCD to obtain a laser-irradiated image of the sample.
  • a laser, a micro-displacement stage, a stage, a filter, and an EMCCD are included.
  • the fiber optic head of the laser is held by a micro-displacement stage to control laser movement.
  • the laser emits laser light from right to left, and the sample is scanned in a plane parallel to the EMCCD.
  • the nano material in the sample is, for example, located in the tumor area of the small animal, and the nano material is excited to be fluorescent and collected by EMCCD.
  • the fluorescence distribution in small animals can be reconstructed by the FDOT reconstruction algorithm.
  • the xy plane is assumed to be a horizontal plane
  • the z-axis is an axis of a vertical horizontal plane
  • the EMCCD, the X-ray source, the laser, and the X-ray flat panel detector are in the xy plane.
  • the EMCCD, the X-ray source, the laser, and the X-ray flat panel detector are not It is limited to the xy plane and can be in a certain plane.
  • the xy plane is taken as an example for description.
  • a laser fiber head is mounted on a two-dimensional micro-displacement stage, and the laser light is incident on the object on the opposite plane of the EMCCD, that is, the xz plane.
  • the laser fiber moves along a set position in a plane, and the movement manner can be various.
  • the position of the laser scanning can be moved by a certain position along the x-axis at a certain distance, and moved N times; the z-axis is at a certain distance.
  • Move one position, move N times form an array of lasers - (N+1) ⁇ (N + 1) matrix; or you can use a method that moves a position at a certain angle along the circumference centered on a certain point.
  • the EMCCD filters the laser and fluorescence through filters, and collects fluorescent images from the body and images that are lasered onto the object.
  • the FDOT three-dimensional reconstruction is performed by the reconstruction algorithm to obtain accurate position information such as the fluorescence distribution in the object.
  • FIG. 5 is a schematic diagram of a method of fluorescence scattering optical tomography according to an embodiment of the present invention. As shown in FIG. 5, the fluorescence scattering optical tomography method may include:
  • Step 501 placing a sample on the stage, the sample is implanted into the nano material, and the nano material emits cold light by X-ray irradiation, and emits fluorescence by laser irradiation;
  • Step 502 Open an X-ray source and an X-ray flat panel detector, the X-ray source emits X-rays to the sample on the stage, the X-ray flat panel detector obtains the CT image of the sample by X-ray irradiation; and the EMCCD obtains the sample by X-ray irradiation.
  • Step 503 Turn off the X-ray source and the X-ray flat panel detector, turn on the laser, and the laser emits laser light to the sample; the EMCCD obtains the laser image and the fluorescent image of the sample irradiated by the laser;
  • Step 504 reconstructing FDOT imaging according to CT imaging, laser image, and fluorescence image.
  • the stage may be a rotating stage; the sample is rotated on the rotating stage; the X-ray flat panel detector obtains the CT image of the sample by X-ray irradiation, which may include: the X-ray flat panel detector obtains the sample in the rotation CT imaging of multiple angles of rotation of the stage; EMCCD obtains X-ray XLCT imaging of the sample, which may include: EMCCD obtains multiple angles of XLCT imaging of the sample rotating on the rotating stage.
  • the fluorescence scattering optical tomography method may further include: the micro-displacement station controls the laser movement by clamping the fiber head of the laser; and the EMCCD obtains the laser-irradiated laser image and the fluorescence image of the sample, which may include: obtaining the sample by the EMCCD A plurality of laser images and fluorescent images of the moving laser light.
  • the EMCCD obtains the laser image and the fluorescence image of the sample, which may include: placing a filter between the EMCCD and the stage, filtering out the fluorescence emitted by the sample by laser irradiation, and obtaining the sample by laser irradiation by EMCCD.
  • the working process in this example may include:
  • the object contains some kind of nano material.
  • the nano material can emit near-infrared fluorescence under the corresponding excitation light source, and can emit cold light under X-ray to adjust the EMCCD field of view. To cover the entire object;
  • the cold light emitted from the sample is collected by EMCCD, and the XLCT image is obtained by the XLCT reconstruction algorithm;
  • the filter and collect the fluorescence image For example, the object is excited at 488 nm, emits fluorescence from 600 nm to 700 nm, and the filter is changed to a long pass filter of 600 nm or higher, so that the EMCCD collects the fluorescent image;
  • Fluorescence and laser images acquired by CT imaging and EMCCD are used as input files of FDOT to reconstruct FDOT imaging.
  • the EMCCD obtains XLCT imaging of the sample by X-ray irradiation, which may include:
  • D(r) is the diffusion coefficient
  • D(r) (3( ⁇ a (r) + (1 - g) ⁇ s (r))) -1
  • ⁇ a (r) is the absorption Coefficient
  • ⁇ s (r) is the scattering coefficient
  • g is the anisotropic parameter
  • ⁇ (r) is the fluorescence intensity
  • S(r) is the light source
  • M is the photon density
  • F is the diffusion coefficient of light divergence
  • is the optical field of view
  • X(r) is the X-ray intensity
  • is the absorption coefficient of light divergence
  • X-rays are emitted from the X-ray source and pass through the object being detected.
  • the object emits near-infrared light as in equation (1):
  • r is the position
  • S(r) is the light source
  • X(r) is the X-ray intensity
  • ⁇ (r) is the nano-optical intensity
  • is the optical field of view.
  • the X-ray intensity distribution is as follows:
  • X 0 is the X-ray intensity at the original position r 0 and ⁇ t ( ⁇ ) is the attenuation coefficient of the X-ray at the position ⁇ .
  • the X-ray intensity X(r) is calculated according to the formula (2).
  • the model of light in biological soft tissue can be obtained by the scattering equation. Because of the high scattering and low absorption of soft tissue in the near infrared field, the transport equation can be expressed as:
  • D(r) is the diffusion coefficient
  • D(r) (3( ⁇ a (r)+(1-g) ⁇ s (r))) -1 ;
  • ⁇ a (r) is the absorption coefficient;
  • ⁇ s (r) is the scattering coefficient;
  • g is the anisotropic parameter;
  • ⁇ (r) is the fluorescence intensity.
  • the finite element method is widely used to solve the scattering equation. According to the finite element theory, the following matrix equation can be obtained:
  • M is the photon density
  • F is the diffusion coefficient of light divergence
  • is the optical field of view
  • X(r) is the X-ray intensity
  • is the absorption coefficient of light divergence.
  • the light emitted from the surface of the object reconstructs the 3D distribution of the X-ray luminescence within the object. Reconstruction is a difficult problem because of the high scattering of light in living tissues. The small timing of collecting data will result in a large number of reconstruction problems.
  • A (M - 1 F) ⁇ ⁇ ⁇ X (r).
  • Equation (5) establishes a linear relationship between sample distribution and near-infrared detection.
  • the reconstruction of the X-ray luminescent sample is to repair the intensity of the X-ray luminescent sample and the intensity of the collected fluorescence.
  • the image can be matched at various angles (space, time) to compensate for the lack of depth information of the FDOT. It is difficult to solve ⁇ from equation (5) because of the presence of noise in the detected data and the morbidity of the reconstruction.
  • X-ray luminescence is sparsely distributed in living organisms, so sparse normalization can be used to solve this problem by minimizing ⁇ :
  • is a normalized parameter
  • FDOT imaging can be reconstructed from CT imaging, laser images, and fluorescent images.
  • the body surface information of the sample can be obtained according to CT imaging;
  • FDOT imaging is reconstructed according to the body surface information of the sample, the position information of the EMCCD, the sample and the laser, and the laser image and the fluorescence image.
  • 360-degree imaging information of the sample is obtained by CT imaging, and body surface information of the sample is generated by toastmakemesh; and the fluorescent image and laser image of the sample are obtained through the experimental steps of FDOT imaging, and the positions of the CCD, the sample, and the laser source are combined.
  • the FDOT reconstruction algorithm can mainly call open source packages such as toast++, wavelet transform, and iso2mesh to complete the entire reconstruction algorithm.
  • Galerkin FEM and zero-order Tikhonov regularization can be used to process the collected sparse fluorescence information matrix.
  • the sample is implanted into the nano material, and the nano material emits cold light by X-ray irradiation, and emits fluorescence by laser irradiation; the X-ray source emits X-rays to the sample, and the X-ray flat panel detector obtains the sample.
  • EMCCD obtains X-ray XLCT imaging of the sample; laser emits laser light to the sample, EMCCD obtains laser image and fluorescence image of the sample; laser image, fluorescence image and CT imaging are used to reconstruct FDOT imaging
  • the FDOT imaging system can be combined with CT and XLCT imaging systems to complete CT, XLCT and FDOT imaging in a short time, shorten the data collection period, and can make up for the deficiencies of FDOT in depth information and obtain more accurate depth information. Reduce the difficulty of reconstruction.
  • embodiments of the present invention can be provided as a method, system, or computer program product. Accordingly, the present invention may take the form of an entirely hardware embodiment, an entirely software embodiment, or a combination of software and hardware. Moreover, the invention can take the form of a computer program product embodied on one or more computer-usable storage media (including but not limited to disk storage, CD-ROM, optical storage, etc.) including computer usable program code.
  • computer-usable storage media including but not limited to disk storage, CD-ROM, optical storage, etc.
  • the computer program instructions can also be stored in a computer readable memory that can direct a computer or other programmable data processing device to operate in a particular manner, such that the instructions stored in the computer readable memory produce an article of manufacture comprising the instruction device.
  • the apparatus implements the functions specified in one or more blocks of a flow or a flow and/or block diagram of the flowchart.
  • These computer program instructions can also be loaded onto a computer or other programmable data processing device such that a series of operational steps are performed on a computer or other programmable device to produce computer-implemented processing for execution on a computer or other programmable device.
  • the instructions provide steps for implementing the functions specified in one or more of the flow or in a block or blocks of a flow diagram.

Abstract

Provided are a fluorescence scatter optical tomography system and a method. The system comprises a stage for supporting a specimen implanted with a nanomaterial emitting cold light by X-ray irradiation, and emitting fluorescence by laser irradiation; an X-ray source for emitting X-rays to the specimen on the stage; an X-ray plate detector for acquiring CT imaging of the specimen by X-ray irradiation; EMCCD for acquiring XLCT imaging of the specimen by X-ray irradiation; and a laser for emitting laser light to the specimen, wherein the EMCCD is also used to acquire the laser image and the fluorescent image of the specimen irradiated by the laser light, and the laser image, the fluorescence image and the CT imaging are used for reconstructing FDOT imaging. The imaging system and method can be used to obtain information with more accurate depth, reduce reconstruction difficulty and shorten the data acquisition cycle.

Description

荧光散射光学断层成像系统及方法Fluorescence scattering optical tomography system and method 技术领域Technical field
本发明涉及医疗影像技术领域,尤其涉及荧光散射光学断层成像系统及方法。The present invention relates to the field of medical imaging technology, and in particular to a fluorescence scattering optical tomography system and method.
背景技术Background technique
荧光散射光学断层成像(Fluorescence Diffuse Optical Tomography,FDOT)技术与MRI、CT、PET相比,具有造价便宜、宜操作、无辐射的优点,常用在小动物活体成像上。FDOT技术的工作原理为,使用激光在某一平面内扫描,事先在小动物体内植入肿瘤和相应靶向荧光试剂,荧光试剂受激光激发,发射近红外光,通过检测器来获得激发光的图片,通过精准三维重建来确定肿瘤在动物体内的位置和分布情况。但是现有的FDOT技术的重建难度较大、在深度信息上往往不准确,采集数据的时间周期较长。Compared with MRI, CT and PET, Fluorescence Diffuse Optical Tomography (FDOT) has the advantages of low cost, easy operation and no radiation. It is commonly used in small animal living imaging. The working principle of FDOT technology is to use laser to scan in a certain plane, implant tumors and corresponding targeted fluorescent reagents in small animals in advance, fluorescent reagents are excited by laser, emit near-infrared light, and obtain excitation light through detectors. Image, through accurate three-dimensional reconstruction to determine the location and distribution of tumors in animals. However, the existing FDOT technology is difficult to reconstruct, and the depth information is often inaccurate, and the time period for collecting data is long.
发明内容Summary of the invention
本发明实施例提供一种荧光散射光学断层成像系统,用以获得较为准确的深度信息,降低重建难度且缩短数据采集周期,该荧光散射光学断层成像系统包括:Embodiments of the present invention provide a fluorescence scattering optical tomography system for obtaining more accurate depth information, reducing reconstruction difficulty, and shortening a data acquisition period. The fluorescence scattering optical tomography system includes:
载物台,用于承载样品,所述样品被植入纳米材料,所述纳米材料经X射线照射发出冷光,经激光照射发出荧光;a stage for carrying a sample, the sample being implanted with a nano material, the nano material emitting cold light by X-ray irradiation, and emitting fluorescence by laser irradiation;
X射线源,用于向所述载物台上的样品发射X射线;An X-ray source for emitting X-rays to a sample on the stage;
X射线平板探测器,用于获得所述样品经X射线照射的CT成像;An X-ray flat panel detector for obtaining CT imaging of the sample by X-ray irradiation;
EMCCD,用于获得所述样品经X射线照射的XLCT成像;EMCCD for obtaining XLCT imaging of the sample by X-ray irradiation;
激光器,用于向所述样品发射激光;a laser for emitting laser light to the sample;
所述EMCCD还用于获得所述样品经激光照射的激光图像和荧光图像,所述激光图像、荧光图像和CT成像用于重建FDOT成像。The EMCCD is also used to obtain laser-irradiated laser images and fluorescent images of the sample, the laser images, fluorescent images, and CT imaging for reconstructing FDOT imaging.
一个实施例中,所述载物台为旋转载物台;所述X射线平板探测器具体用于获得所述样品在旋转载物台旋转的多个角度的CT成像;所述EMCCD具体用于获得所述样品在旋转载物台旋转的多个角度的XLCT成像。In one embodiment, the stage is a rotating stage; the X-ray flat panel detector is specifically configured to obtain CT imaging of a plurality of angles of rotation of the sample on a rotating stage; the EMCCD is specifically used for XLCT imaging of the plurality of angles at which the sample is rotated on the rotating stage is obtained.
一个实施例中,该荧光散射光学断层成像系统还包括:In one embodiment, the fluorescence scattering optical tomography system further comprises:
微位移台,用于通过夹持激光器的光纤头来控制激光移动;所述EMCCD具体用于获得所述样品经移动的激光照射的多个激光图像和荧光图像。 A micro-displacement stage for controlling laser movement by clamping a fiber optic head of the laser; the EMCCD is specifically for obtaining a plurality of laser images and fluorescent images of the sample irradiated by the moving laser.
一个实施例中,该荧光散射光学断层成像系统还包括:In one embodiment, the fluorescence scattering optical tomography system further comprises:
设于EMCCD与载物台之间的滤光片,用于滤除所述样品经激光照射发出的荧光,使EMCCD获得所述样品经激光照射的激光图像;滤除所述激光器发出的激光,使EMCCD获得所述样品经激光照射的荧光图像。a filter disposed between the EMCCD and the stage for filtering the fluorescence emitted by the sample by laser irradiation, so that the EMCCD obtains a laser image of the sample irradiated by the laser; filtering the laser emitted by the laser, The EMCCD was subjected to a laser-irradiated fluorescence image of the sample.
本发明实施例还提供一种荧光散射光学断层成像方法,用以获得较为准确的深度信息,降低重建难度且缩短数据采集周期,该荧光散射光学断层成像方法包括:Embodiments of the present invention further provide a fluorescence scattering optical tomography method for obtaining more accurate depth information, reducing reconstruction difficulty, and shortening a data acquisition period. The fluorescence scattering optical tomography method includes:
在载物台上放置样品,所述样品被植入纳米材料,所述纳米材料经X射线照射发出冷光,经激光照射发出荧光;Placing a sample on a stage, the sample being implanted with a nano material that emits luminescence by X-ray irradiation and emits fluorescence by laser irradiation;
打开X射线源及X射线平板探测器,X射线源向所述载物台上的样品发射X射线,X射线平板探测器获得所述样品经X射线照射的CT成像;EMCCD获得所述样品经X射线照射的XLCT成像;Opening an X-ray source and an X-ray flat panel detector, the X-ray source emitting X-rays to the sample on the stage, and the X-ray flat panel detector obtains CT imaging of the sample by X-ray irradiation; the EMCCD obtains the sample by X-ray irradiation of XLCT imaging;
关闭X射线源及X射线平板探测器,打开激光器,激光器向所述样品发射激光;EMCCD获得所述样品经激光照射的激光图像和荧光图像;Turning off the X-ray source and the X-ray flat panel detector, turning on the laser, and the laser emitting laser light to the sample; the EMCCD obtains the laser image and the fluorescent image of the sample irradiated by the laser;
根据所述CT成像、激光图像和荧光图像,重建得到FDOT成像。According to the CT imaging, the laser image, and the fluorescence image, FDOT imaging is reconstructed.
一个实施例中,所述载物台为旋转载物台;所述样品在旋转载物台上旋转;In one embodiment, the stage is a rotating stage; the sample is rotated on a rotating stage;
X射线平板探测器获得所述样品经X射线照射的CT成像,包括:X射线平板探测器获得所述样品在旋转载物台旋转的多个角度的CT成像;An X-ray flat panel detector obtains CT imaging of the sample by X-ray irradiation, comprising: an X-ray flat panel detector obtaining CT images of the plurality of angles of rotation of the sample on the rotating stage;
EMCCD获得所述样品经X射线照射的XLCT成像,包括:EMCCD获得所述样品在旋转载物台旋转的多个角度的XLCT成像。The EMCCD obtains X-ray illuminated XLCT imaging of the sample, including: EMCCD obtains multiple angles of XLCT imaging of the sample rotating on a rotating stage.
一个实施例中,EMCCD获得所述样品经X射线照射的XLCT成像,包括:In one embodiment, the EMCCD obtains X-ray illuminated XLCT imaging of the sample, including:
通过有限元方法解散射方程
Figure PCTCN2016087425-appb-000001
得到矩阵方程M·φ(r)=F·ε·X(r)·ρ,再通过稀疏矩阵归一化法解
Figure PCTCN2016087425-appb-000002
最小化问题,得到ρ;根据ρ重建XLCT成像;
Solving the scattering equation by finite element method
Figure PCTCN2016087425-appb-000001
Obtain the matrix equation M·φ(r)=F·ε·X(r)·ρ, and then solve it by sparse matrix normalization method.
Figure PCTCN2016087425-appb-000002
Minimize the problem, get ρ; reconstruct XLCT imaging according to ρ;
其中,r是位置;D(r)是扩散系数,D(r)=(3(μa(r)+(1-g)μs(r)))-1;μa(r)是吸收系数;μs(r)是散射系数;g是各项异性参数;φ(r)是荧光强度;S(r)是光源;Where r is the position; D(r) is the diffusion coefficient, D(r) = (3(μ a (r) + (1 - g) μ s (r))) -1 ; μ a (r) is the absorption Coefficient; μ s (r) is the scattering coefficient; g is the anisotropic parameter; φ(r) is the fluorescence intensity; S(r) is the light source;
M是光子密度;F是光发散的扩散系数;ε是光学视野;X(r)是X射线强度;ρ是光发散的吸收系数;M is the photon density; F is the diffusion coefficient of light divergence; ε is the optical field of view; X(r) is the X-ray intensity; ρ is the absorption coefficient of light divergence;
A=(M-1F)·ε·X(r);Φ=A·ρ;λ是归一性参数。 A = (M - 1 F) · ε · X (r); Φ = A · ρ; λ is a normalized parameter.
一个实施例中,该荧光散射光学断层成像方法进一步包括:微位移台通过夹持激光器的光纤头来控制激光移动;In one embodiment, the fluorescence scattering optical tomography method further comprises: the micro-displacement station controls laser movement by clamping a fiber tip of the laser;
EMCCD获得所述样品经激光照射的激光图像和荧光图像,包括:EMCCD获得所述样品经移动的激光照射的多个激光图像和荧光图像。The EMCCD obtains a laser-irradiated laser image and a fluorescent image of the sample, including: EMCCD obtains a plurality of laser images and fluorescent images of the sample irradiated by the moving laser.
一个实施例中,EMCCD获得所述样品经激光照射的激光图像和荧光图像,包括:In one embodiment, the EMCCD obtains laser-irradiated laser images and fluorescent images of the sample, including:
在EMCCD与载物台之间放置滤光片,滤除所述样品经激光照射发出的荧光,EMCCD获得所述样品经激光照射的激光图像;A filter is placed between the EMCCD and the stage to filter out the fluorescence emitted by the sample by laser irradiation, and the EMCCD obtains a laser image of the sample irradiated by the laser;
更换滤光片,滤除所述激光器发出的激光,EMCCD获得所述样品经激光照射的荧光图像。The filter is replaced, the laser light emitted by the laser is filtered out, and the EMCCD obtains a fluorescent image of the sample irradiated with laser light.
一个实施例中,根据所述CT成像、激光图像和荧光图像,重建得到FDOT成像,包括:In one embodiment, FDOT imaging is reconstructed based on the CT imaging, laser image, and fluorescence image, including:
根据所述CT成像得到所述样品的体表面信息;Obtaining body surface information of the sample according to the CT imaging;
根据所述样品的体表面信息,所述EMCCD、样品和激光器的位置信息,以及所述激光图像和荧光图像,重建得到FDOT成像。The FDOT imaging is reconstructed based on the body surface information of the sample, the position information of the EMCCD, the sample and the laser, and the laser image and the fluorescence image.
本发明实施例中,样品植入纳米材料,该纳米材料经X射线照射发出冷光,经激光照射发出荧光;X射线源向样品发射X射线,X射线平板探测器获得样品经X射线照射的CT成像,EMCCD获得样品经X射线照射的XLCT成像;激光器向样品发射激光,EMCCD获得样品经激光照射的激光图像和荧光图像;激光图像、荧光图像和CT成像用来重建FDOT成像,使FDOT成像系统与CT、XLCT成像系统相融合,可以在短时间内完成CT、XLCT和FDOT成像,缩短数据采集周期,并且可以弥补FDOT在深度信息上的不足,获得较为准确的深度信息,降低重建难度。In the embodiment of the invention, the sample is implanted into the nano material, and the nano material emits cold light by X-ray irradiation, and emits fluorescence by laser irradiation; the X-ray source emits X-rays to the sample, and the X-ray flat panel detector obtains the X-ray irradiated sample by the X-ray flat panel detector. Imaging, EMCCD obtains X-ray XLCT imaging of the sample; laser emits laser light to the sample, EMCCD obtains laser-irradiated laser image and fluorescence image of the sample; laser image, fluorescence image and CT imaging are used to reconstruct FDOT imaging, and FDOT imaging system Combined with CT and XLCT imaging systems, CT, XLCT and FDOT imaging can be completed in a short time, shortening the data acquisition period, and can make up for the deficiencies of FDOT in depth information, obtain more accurate depth information, and reduce reconstruction difficulty.
附图说明DRAWINGS
为了更清楚地说明本发明实施例中的技术方案,下面将对实施例描述中所需要使用的附图作简单地介绍,显而易见地,下面描述中的附图仅仅是本发明的一些实施例,对于本领域普通技术人员来讲,在不付出创造性劳动的前提下,还可以根据这些附图获得其他的附图。在附图中:In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly described below. It is obvious that the drawings in the following description are only some embodiments of the present invention. Other drawings may also be obtained from those of ordinary skill in the art in light of the inventive work. In the drawing:
图1为本发明实施例中荧光散射光学断层成像系统的示意图;1 is a schematic view of a fluorescence scattering optical tomography system according to an embodiment of the present invention;
图2为本发明实施例中荧光散射光学断层成像系统分解的CT成像系统示意图;2 is a schematic diagram of a CT imaging system exploded by a fluorescence scattering optical tomography system according to an embodiment of the present invention;
图3为本发明实施例中荧光散射光学断层成像系统分解的XLCT成像系统示意图; 3 is a schematic diagram of an XLCT imaging system exploded by a fluorescence scattering optical tomography system according to an embodiment of the present invention;
图4为本发明实施例中荧光散射光学断层成像系统分解的FDOT成像系统示意图;4 is a schematic diagram of an FDOT imaging system exploded by a fluorescence scattering optical tomography system according to an embodiment of the present invention;
图5为本发明实施例中荧光散射光学断层成像方法的示意图。FIG. 5 is a schematic diagram of a method of fluorescence scattering optical tomography according to an embodiment of the present invention.
具体实施方式Detailed ways
为使本发明实施例的目的、技术方案和优点更加清楚明白,下面结合附图对本发明实施例做进一步详细说明。在此,本发明的示意性实施例及其说明用于解释本发明,但并不作为对本发明的限定。The embodiments of the present invention will be further described in detail below with reference to the accompanying drawings. The illustrative embodiments of the present invention and the description thereof are intended to explain the present invention, but are not intended to limit the invention.
为了获得较为准确的深度信息,降低重建难度且缩短数据采集周期,本发明实施例提供一种荧光散射光学断层成像系统,该荧光散射光学断层成像系统将FDOT成像技术与CT(Computed Tomography,电子计算机断层扫描)成像技术、XLCT(X射线激发冷光断层成像,X-ray Luminescence Computed Tomography))成像技术在空间上相融合,以CT、XLCT成像融合FDOT成像,弥补FDOT成像在深度信息上的不足,从而在重建后得到精准的肿瘤分布深度信息,大幅度地提高成像质量,降低重建难度且缩短数据采集周期。其中CT成像作为FDOT成像采集数据的先验信息,FDOT系统与CT成像系统融合,可以使FDOT成像系统所提供的功能图像在与CT成像进行比较和处理的过程中,借助由CT成像所提供的空间结构而更直观准确地被呈现出来,XLCT成像系统与FDOT成像系统在空间上融合,可以得到准确的先验信息与荧光信息。In order to obtain more accurate depth information, reduce reconstruction difficulty, and shorten data collection period, embodiments of the present invention provide a fluorescence scattering optical tomography system that combines FDOT imaging technology with CT (Computed Tomography). Tomography) XLCT (X-ray Luminescence Computed Tomography) imaging technology is spatially fused, and FDOT imaging is combined with CT and XLCT imaging to compensate for the lack of depth information in FDOT imaging. Therefore, accurate reconstruction of tumor distribution depth information is obtained after reconstruction, which greatly improves imaging quality, reduces reconstruction difficulty, and shortens data collection period. CT imaging is used as a priori information for FDOT imaging data acquisition. The FDOT system is integrated with the CT imaging system, which enables the functional images provided by the FDOT imaging system to be compared and processed by CT imaging, with the aid of CT imaging. The spatial structure is presented more intuitively and accurately. The XLCT imaging system and the FDOT imaging system are spatially fused to obtain accurate prior information and fluorescence information.
图1为本发明实施例中荧光散射光学断层成像系统的示意图。如图1所示,本发明实施例中荧光散射光学断层成像系统可以包括:1 is a schematic diagram of a fluorescence scattering optical tomography system in accordance with an embodiment of the present invention. As shown in FIG. 1, the fluorescence scattering optical tomography system in the embodiment of the present invention may include:
载物台,用于承载样品,该样品被植入纳米材料,该纳米材料经X射线照射发出冷光,经激光照射发出荧光;a stage for carrying a sample, the sample being implanted with a nano material, the nano material being luminescence by X-ray irradiation, and emitting fluorescence by laser irradiation;
X射线源,用于向载物台上的样品发射X射线;An X-ray source for emitting X-rays to a sample on the stage;
X射线平板探测器,用于获得样品经X射线照射的CT成像;X-ray flat panel detector for obtaining CT image of X-ray irradiation of the sample;
EMCCD,用于获得样品经X射线照射的XLCT成像;EMCCD for obtaining XLCT imaging of X-rays of samples;
激光器,用于向样品发射激光;a laser for emitting laser light to the sample;
EMCCD还用于获得样品经激光照射的激光图像和荧光图像,激光图像、荧光图像和CT成像用于重建FDOT成像。The EMCCD is also used to obtain laser-irradiated laser images and fluorescence images of samples, laser images, fluorescence images, and CT imaging for reconstruction of FDOT imaging.
由图1所示结构可以得知,本发明实施例的荧光散射光学断层成像系统采用了将FDOT成像系统与CT成像系统和XLCT成像系统相融合的方式,在短时间内完成XLCT、FDOT、CT成像,将CT成像、XLCT成像与FDOT成像融合。如图2-4所示, 该荧光散射光学断层成像系统可以分解为CT成像系统、XLCT成像系统和FDOT成像系统。It can be known from the structure shown in FIG. 1 that the fluorescence scattering optical tomography system of the embodiment of the present invention adopts a method of combining an FDOT imaging system with a CT imaging system and an XLCT imaging system, and completes XLCT, FDOT, and CT in a short time. Imaging, fusion of CT imaging, XLCT imaging and FDOT imaging. As shown in Figure 2-4, The fluorescence scattering optical tomography system can be decomposed into a CT imaging system, an XLCT imaging system, and an FDOT imaging system.
图2为本发明实施例中荧光散射光学断层成像系统分解的CT成像系统示意图。如图2所示,该分解的CT成像系统包括X射线源和X射线平板探测器。由X射线源发出X射线,X射线平板探测器检测到X射线信号,重建得到CT成像。2 is a schematic diagram of a CT imaging system exploded by a fluorescence scattering optical tomography system according to an embodiment of the present invention. As shown in Figure 2, the exploded CT imaging system includes an X-ray source and an X-ray flat panel detector. The X-ray is emitted by the X-ray source, the X-ray flat panel detector detects the X-ray signal, and the CT image is reconstructed.
图3为本发明实施例中荧光散射光学断层成像系统分解的XLCT成像系统示意图。如图3所示,该分解的XLCT成像系统包括X射线源和EMCCD(CCD相机)。图3中还包括了滤光片。X射线源向样品发射X射线,样品中的纳米材料经X射线照射发出冷光,EMCCD采集冷光,重建出XLCT成像。XLCT技术是当前科学研究的热门,为X射线分子影像开创了新的可能。在XLCT成像系统中,纳米材料可以在X射线下激发出近红外光,因为X射线和近红外光在组织内有长的穿透性,它们很适于在生物体内成像。在XLCT成像系统中,断层图像从一系列的X射线激发获得冷光,被高灵敏度的CCD(Charge-Coupled Device)获得。最近,大量的研究放在通过纳米材料的特性提升生物影像。3 is a schematic diagram of an XLCT imaging system exploded by a fluorescence scattering optical tomography system according to an embodiment of the present invention. As shown in Figure 3, the exploded XLCT imaging system includes an X-ray source and an EMCCD (CCD camera). A filter is also included in FIG. The X-ray source emits X-rays to the sample, the nano-materials in the sample are luminescence by X-ray irradiation, and the EMCCD collects luminescence to reconstruct XLCT imaging. XLCT technology is a hot topic in current scientific research, opening up new possibilities for X-ray molecular imaging. In XLCT imaging systems, nanomaterials can excite near-infrared light under X-rays, and because X-rays and near-infrared light have long penetrability in tissues, they are well suited for imaging in vivo. In the XLCT imaging system, the tomographic image is obtained from a series of X-ray excitations and is obtained by a highly sensitive CCD (Charge-Coupled Device). Recently, a large number of studies have focused on improving biological imaging through the properties of nanomaterials.
图4为本发明实施例中荧光散射光学断层成像系统分解的FDOT成像系统示意图。如图4所示,该分解的FDOT成像系统包括激光器和EMCCD。激光器向样品发射激光,样品中的纳米材料经激光照射发出荧光,EMCCD获得采集样品的激光图像和荧光图像。图4中还示出了可能包含的准直器,激光器为近红外激光器。4 is a schematic diagram of an FDOT imaging system exploded by a fluorescence scattering optical tomography system according to an embodiment of the present invention. As shown in Figure 4, the exploded FDOT imaging system includes a laser and an EMCCD. The laser emits a laser to the sample, and the nanomaterial in the sample is irradiated with laser light to emit fluorescence, and the EMCCD obtains a laser image and a fluorescent image of the collected sample. Also shown in Figure 4 is a collimator that may be included, the laser being a near infrared laser.
具体实施时,载物台可以是旋转载物台,X射线平板探测器可以获得样品在旋转载物台旋转的多个角度的CT成像,EMCCD可以获得样品在旋转载物台旋转的多个角度的XLCT成像。例如在图3所示的分解的XLCT成像系统中,由X射线源激发样品中的纳米材料发出冷光,样品在载物台上旋转,EMCCD获得各个角度的样品冷光成像。In a specific implementation, the stage can be a rotating stage, and the X-ray flat panel detector can obtain CT imaging of the plurality of angles of the sample rotating on the rotating stage, and the EMCCD can obtain multiple angles of the sample rotating on the rotating stage. XLCT imaging. For example, in the exploded XLCT imaging system shown in Figure 3, the nanomaterial in the sample is excited by the X-ray source to emit luminescence, the sample is rotated on the stage, and the EMCCD obtains luminescence imaging of the sample at various angles.
具体实施时,本发明实施例的荧光散射光学断层成像系统还可以包括:微位移台,用于通过夹持激光器的光纤头来控制激光移动;EMCCD具体用于获得样品经移动的激光照射的多个激光图像和荧光图像。In a specific implementation, the fluorescence scattering optical tomography system of the embodiment of the present invention may further include: a micro-displacement stage for controlling laser movement by clamping a fiber head of the laser; and the EMCCD is specifically used for obtaining a laser beam irradiated by the sample. Laser images and fluorescent images.
具体实施时,本发明实施例的荧光散射光学断层成像系统还可以包括:设于EMCCD与载物台之间的滤光片,用于滤除样品经激光照射发出的荧光,使EMCCD获得样品经激光照射的激光图像;滤除激光器发出的激光,使EMCCD获得样品经激光照射的荧光图像。 In a specific implementation, the fluorescence scattering optical tomography system of the embodiment of the present invention may further include: a filter disposed between the EMCCD and the stage for filtering the fluorescence emitted by the sample by the laser, so that the EMCCD obtains the sample. Laser-irradiated laser image; filtering out the laser from the laser, allowing EMCCD to obtain a laser-irradiated image of the sample.
例如,在图4所示的分解的FDOT成像系统中,包括了激光器、微位移台、载物台、滤波片和EMCCD。由微位移台夹持激光器的光纤头来控制激光移动。再如图1所示,激光器从右往左发射激光,在平行于EMCCD的平面内扫描到样品,样品中纳米材料例如位于小动物的肿瘤区域,纳米材料被激发出荧光并由EMCCD采集,最后通过FDOT重建算法可以重建出小动物体内的荧光分布。For example, in the exploded FDOT imaging system shown in FIG. 4, a laser, a micro-displacement stage, a stage, a filter, and an EMCCD are included. The fiber optic head of the laser is held by a micro-displacement stage to control laser movement. As shown in Fig. 1, the laser emits laser light from right to left, and the sample is scanned in a plane parallel to the EMCCD. The nano material in the sample is, for example, located in the tumor area of the small animal, and the nano material is excited to be fluorescent and collected by EMCCD. The fluorescence distribution in small animals can be reconstructed by the FDOT reconstruction algorithm.
实施例中,假定xy平面为水平面,z轴为垂直水平面的轴,EMCCD、X射线源、激光器、X射线平板探测器在xy平面,当然EMCCD、X射线源、激光器、X射线平板探测器不限于在xy平面,在某个平面内即可,此处以在xy平面为例进行说明。由二维微位移台搭载激光光纤头,激光在EMCCD相对的平面即xz平面上照到物体上。激光光纤在一个平面内沿设定好的位置移动,移动方式可以有多种,例如,激光扫描的位置可以采用沿x轴每隔一定距离移动一个位置,移动N次;z轴每隔一定距离移动一个位置,移动N次,形成激光的阵列——(N+1)×(N+1)的矩阵;或者可以采用以某一点为圆心,沿着圆周每隔一定角度移动一个位置的方法。EMCCD通过滤光片,分别滤掉激光和荧光,采集物体体内发出的荧光图像和激光照到物体上的图像。通过重建算法进行FDOT三维重建,得到物体内荧光分布等精准位置信息。In the embodiment, the xy plane is assumed to be a horizontal plane, the z-axis is an axis of a vertical horizontal plane, and the EMCCD, the X-ray source, the laser, and the X-ray flat panel detector are in the xy plane. Of course, the EMCCD, the X-ray source, the laser, and the X-ray flat panel detector are not It is limited to the xy plane and can be in a certain plane. Here, the xy plane is taken as an example for description. A laser fiber head is mounted on a two-dimensional micro-displacement stage, and the laser light is incident on the object on the opposite plane of the EMCCD, that is, the xz plane. The laser fiber moves along a set position in a plane, and the movement manner can be various. For example, the position of the laser scanning can be moved by a certain position along the x-axis at a certain distance, and moved N times; the z-axis is at a certain distance. Move one position, move N times, form an array of lasers - (N+1) × (N + 1) matrix; or you can use a method that moves a position at a certain angle along the circumference centered on a certain point. The EMCCD filters the laser and fluorescence through filters, and collects fluorescent images from the body and images that are lasered onto the object. The FDOT three-dimensional reconstruction is performed by the reconstruction algorithm to obtain accurate position information such as the fluorescence distribution in the object.
图5为本发明实施例中荧光散射光学断层成像方法的示意图。如图5所示,该荧光散射光学断层成像方法可以包括:FIG. 5 is a schematic diagram of a method of fluorescence scattering optical tomography according to an embodiment of the present invention. As shown in FIG. 5, the fluorescence scattering optical tomography method may include:
步骤501、在载物台上放置样品,该样品被植入纳米材料,该纳米材料经X射线照射发出冷光,经激光照射发出荧光;Step 501: placing a sample on the stage, the sample is implanted into the nano material, and the nano material emits cold light by X-ray irradiation, and emits fluorescence by laser irradiation;
步骤502、打开X射线源及X射线平板探测器,X射线源向载物台上的样品发射X射线,X射线平板探测器获得样品经X射线照射的CT成像;EMCCD获得样品经X射线照射的XLCT成像;Step 502: Open an X-ray source and an X-ray flat panel detector, the X-ray source emits X-rays to the sample on the stage, the X-ray flat panel detector obtains the CT image of the sample by X-ray irradiation; and the EMCCD obtains the sample by X-ray irradiation. XLCT imaging;
步骤503、关闭X射线源及X射线平板探测器,打开激光器,激光器向样品发射激光;EMCCD获得样品经激光照射的激光图像和荧光图像;Step 503: Turn off the X-ray source and the X-ray flat panel detector, turn on the laser, and the laser emits laser light to the sample; the EMCCD obtains the laser image and the fluorescent image of the sample irradiated by the laser;
步骤504、根据CT成像、激光图像和荧光图像,重建得到FDOT成像。Step 504: reconstructing FDOT imaging according to CT imaging, laser image, and fluorescence image.
具体实施时,载物台可以为旋转载物台;样品在旋转载物台上旋转;X射线平板探测器获得样品经X射线照射的CT成像,可以包括:X射线平板探测器获得样品在旋转载物台旋转的多个角度的CT成像;EMCCD获得样品经X射线照射的XLCT成像,可以包括:EMCCD获得样品在旋转载物台旋转的多个角度的XLCT成像。 In a specific implementation, the stage may be a rotating stage; the sample is rotated on the rotating stage; the X-ray flat panel detector obtains the CT image of the sample by X-ray irradiation, which may include: the X-ray flat panel detector obtains the sample in the rotation CT imaging of multiple angles of rotation of the stage; EMCCD obtains X-ray XLCT imaging of the sample, which may include: EMCCD obtains multiple angles of XLCT imaging of the sample rotating on the rotating stage.
具体实施时,该荧光散射光学断层成像方法可以进一步包括:微位移台通过夹持激光器的光纤头来控制激光移动;EMCCD获得样品经激光照射的激光图像和荧光图像,可以包括:EMCCD获得样品经移动的激光照射的多个激光图像和荧光图像。In a specific implementation, the fluorescence scattering optical tomography method may further include: the micro-displacement station controls the laser movement by clamping the fiber head of the laser; and the EMCCD obtains the laser-irradiated laser image and the fluorescence image of the sample, which may include: obtaining the sample by the EMCCD A plurality of laser images and fluorescent images of the moving laser light.
具体实施时,EMCCD获得样品经激光照射的激光图像和荧光图像,可以包括:在EMCCD与载物台之间放置滤光片,滤除样品经激光照射发出的荧光,EMCCD获得样品经激光照射的激光图像;更换滤光片,滤除激光器发出的激光,EMCCD获得样品经激光照射的荧光图像。In the specific implementation, the EMCCD obtains the laser image and the fluorescence image of the sample, which may include: placing a filter between the EMCCD and the stage, filtering out the fluorescence emitted by the sample by laser irradiation, and obtaining the sample by laser irradiation by EMCCD. The laser image; the filter is replaced, the laser from the laser is filtered out, and the EMCCD obtains a fluorescent image of the sample after laser irradiation.
下面给出一个具体实例说明本发明实施例中荧光散射光学断层成像方法的工作过程,本例中工作过程可以包括:A specific example is given below to illustrate the working process of the fluorescence scattering optical tomography method in the embodiment of the present invention. The working process in this example may include:
1、先在旋转载物台上放置需被重建的物体,物体内含有某种纳米材料,该纳米材料在相应激发光源下能够发出近红外的荧光,在X射线下可以发出冷光,调整EMCCD视野至能够覆盖整个物体;1. First place the object to be reconstructed on the rotating stage. The object contains some kind of nano material. The nano material can emit near-infrared fluorescence under the corresponding excitation light source, and can emit cold light under X-ray to adjust the EMCCD field of view. To cover the entire object;
2、打开X射线源和X射线平板探测器;2. Open the X-ray source and the X-ray flat panel detector;
3、使旋转载物台以一定速度旋转,由X射线平板探测器采集到样品图像,重建出样品的CT成像;3. Rotating the rotating stage at a certain speed, and collecting the sample image by the X-ray flat panel detector to reconstruct the CT image of the sample;
4、同时由EMCCD采集样品上发出的冷光,由XLCT重建算法得到XLCT成像;4. At the same time, the cold light emitted from the sample is collected by EMCCD, and the XLCT image is obtained by the XLCT reconstruction algorithm;
5、关闭X射线源和X射线平板探测器;5. Turn off the X-ray source and the X-ray flat panel detector;
6、打开激光器;6. Turn on the laser;
7、操作夹持激光器光纤的二维微位移台,使之按预设方式移动,即移动激光光纤头的位置,使之在不同的位置发射激光;7. operating a two-dimensional micro-displacement stage holding the laser fiber to move in a preset manner, that is, moving the position of the laser fiber head to emit laser light at different positions;
8、在EMCCD前放上滤光片,滤掉物体发出的荧光,只采集激光图像,例如物体在488nm下受到激发,发出600nm-700nm的荧光,首先放置的滤光片为488nm窄带通(通带10nm)的滤光片,只让EMCCD采集到488nm的光线;8. Put a filter on the EMCCD to filter out the fluorescence emitted by the object. Only the laser image is collected. For example, the object is excited at 488 nm, and the fluorescence is emitted from 600 nm to 700 nm. The first filter is 488 nm narrow band pass. With 10nm) filter, only EMCCD collects 488nm light;
9、更改滤光片,采集荧光图像,例如物体在488nm下受到激发,发出600nm-700nm的荧光,更改滤光片为600nm以上长通的滤光片,使EMCCD采集到荧光图像;9. Change the filter and collect the fluorescence image. For example, the object is excited at 488 nm, emits fluorescence from 600 nm to 700 nm, and the filter is changed to a long pass filter of 600 nm or higher, so that the EMCCD collects the fluorescent image;
10、由CT成像、EMCCD采集的荧光、激光图像,作为FDOT的输入文件,重建得到FDOT成像。10. Fluorescence and laser images acquired by CT imaging and EMCCD are used as input files of FDOT to reconstruct FDOT imaging.
具体实施时,EMCCD获得样品经X射线照射的XLCT成像,可以包括: In specific implementation, the EMCCD obtains XLCT imaging of the sample by X-ray irradiation, which may include:
通过有限元方法解散射方程
Figure PCTCN2016087425-appb-000003
得到矩阵方程M·φ(r)=F·ε·X(r)·ρ,再通过稀疏矩阵归一化法解
Figure PCTCN2016087425-appb-000004
最小化问题,得到ρ;根据ρ重建XLCT成像;
Solving the scattering equation by finite element method
Figure PCTCN2016087425-appb-000003
Obtain the matrix equation M·φ(r)=F·ε·X(r)·ρ, and then solve it by sparse matrix normalization method.
Figure PCTCN2016087425-appb-000004
Minimize the problem, get ρ; reconstruct XLCT imaging according to ρ;
其中,r是位置;D(r)是扩散系数,D(r)=(3(μa(r)+(1-g)μs(r)))-1;μa(r)是吸收系数;μs(r)是散射系数;g是各项异性参数;φ(r)是荧光强度;S(r)是光源;Where r is the position; D(r) is the diffusion coefficient, D(r) = (3(μ a (r) + (1 - g) μ s (r))) -1 ; μ a (r) is the absorption Coefficient; μ s (r) is the scattering coefficient; g is the anisotropic parameter; φ(r) is the fluorescence intensity; S(r) is the light source;
M是光子密度;F是光发散的扩散系数;ε是光学视野;X(r)是X射线强度;ρ是光发散的吸收系数;M is the photon density; F is the diffusion coefficient of light divergence; ε is the optical field of view; X(r) is the X-ray intensity; ρ is the absorption coefficient of light divergence;
A=(M-1F)·ε·X(r);Φ=A·ρ;λ是归一性参数。A = (M - 1 F) · ε · X (r); Φ = A · ρ; λ is a normalized parameter.
下面详细介绍XLCT成像系统重建XLCT成像的过程及原理:The process and principle of reconstructing XLCT imaging in the XLCT imaging system are detailed below:
X射线从X射线源发出,穿过被检测的物体。当X射线穿过物体时,物体发出近红外光如公式(1):X-rays are emitted from the X-ray source and pass through the object being detected. When an X-ray passes through an object, the object emits near-infrared light as in equation (1):
S(r)=εX(r)ρ(r)           (1)S(r)=εX(r)ρ(r) (1)
其中,r是位置,S(r)是光源,X(r)是X射线强度,ρ(r)是纳米光学强度,ε是光学视野。Where r is the position, S(r) is the light source, X(r) is the X-ray intensity, ρ(r) is the nano-optical intensity, and ε is the optical field of view.
根据lambert-beers准则,当X射线穿过物体时,X射线强度分布如下:According to the lambert-beers criterion, when X-rays pass through an object, the X-ray intensity distribution is as follows:
Figure PCTCN2016087425-appb-000005
Figure PCTCN2016087425-appb-000005
其中,X0是在原始位置r0的X射线强度,μt(τ)是X射线在位置τ的衰减系数。X射线强度X(r)根据公式(2)计算得到。Where X 0 is the X-ray intensity at the original position r 0 and μ t (τ) is the attenuation coefficient of the X-ray at the position τ. The X-ray intensity X(r) is calculated according to the formula (2).
光线在生物软体组织中的模型可以通过散射方程得到。因为软组织在近红外领域的高散射性和低吸收性,传输方程可以表达为:The model of light in biological soft tissue can be obtained by the scattering equation. Because of the high scattering and low absorption of soft tissue in the near infrared field, the transport equation can be expressed as:
Figure PCTCN2016087425-appb-000006
Figure PCTCN2016087425-appb-000006
其中,D(r)是扩散系数,D(r)=(3(μa(r)+(1-g)μs(r)))-1;μa(r)是吸收系数;μs(r)是散射系数;g是各项异性参数;φ(r)是荧光强度。Where D(r) is the diffusion coefficient, D(r)=(3(μ a (r)+(1-g)μ s (r))) -1 ; μ a (r) is the absorption coefficient; μ s (r) is the scattering coefficient; g is the anisotropic parameter; φ(r) is the fluorescence intensity.
有限元方法广泛用来解散射方程,根据有限元理论,可以获得如下矩阵方程:The finite element method is widely used to solve the scattering equation. According to the finite element theory, the following matrix equation can be obtained:
M·φ(r)=F·ε·X(r)·ρ          (4)M·φ(r)=F·ε·X(r)·ρ (4)
其中,M是光子密度;F是光发散的扩散系数;ε是光学视野;X(r)是X射线强度;ρ是光发散的吸收系数。 Where M is the photon density; F is the diffusion coefficient of light divergence; ε is the optical field of view; X(r) is the X-ray intensity; and ρ is the absorption coefficient of light divergence.
在上面的光学传输方程基础上,从物体表面发射的光,重建了X射线冷光在物体内的3D分布。因为光在生物体组织的高散射性,重建是一个困难的问题。在采集数据的微小的时序将导致大量的重建问题。Based on the above optical transmission equation, the light emitted from the surface of the object reconstructs the 3D distribution of the X-ray luminescence within the object. Reconstruction is a difficult problem because of the high scattering of light in living tissues. The small timing of collecting data will result in a large number of reconstruction problems.
因为矩阵M在公式(4)中是有限的;Because the matrix M is finite in equation (4);
Φ=A·ρ            (5)Φ=A·ρ (5)
这里,A=(M-1F)·ε·X(r)。Here, A = (M - 1 F) · ε · X (r).
公式(5)在样品分布和近红外检测之间建立了线性关系。X射线冷光样品的重建是修复了X射线冷光样品的强度和采集到的荧光强度。通过将XLCT成像系统与FDOT成像系统融合,同时采集荧光信息和近红外冷光信息,可以使得图像能够在各个角度(空间、时间)上匹配,弥补FDOT在深度信息上的不足。因为在检测数据中存在噪声,和重建的病态性,从公式(5)中很难解出ρ。在大多数的生物应用中,X射线冷光在生物体内稀疏分布,所以稀疏归一化法可以被用于解决这个问题,通过最小化下式得到ρ:Equation (5) establishes a linear relationship between sample distribution and near-infrared detection. The reconstruction of the X-ray luminescent sample is to repair the intensity of the X-ray luminescent sample and the intensity of the collected fluorescence. By combining the XLCT imaging system with the FDOT imaging system, and simultaneously acquiring fluorescence information and near-infrared luminescence information, the image can be matched at various angles (space, time) to compensate for the lack of depth information of the FDOT. It is difficult to solve ρ from equation (5) because of the presence of noise in the detected data and the morbidity of the reconstruction. In most biological applications, X-ray luminescence is sparsely distributed in living organisms, so sparse normalization can be used to solve this problem by minimizing ρ:
Figure PCTCN2016087425-appb-000007
Figure PCTCN2016087425-appb-000007
λ是归一性参数。λ is a normalized parameter.
在获得CT成像、激光图像和荧光图像后,可以根据CT成像、激光图像和荧光图像,重建得到FDOT成像。具体的,可以根据CT成像得到样品的体表面信息;根据样品的体表面信息,EMCCD、样品和激光器的位置信息,以及激光图像和荧光图像,重建得到FDOT成像。例如,首先通过CT成像,得到样品360度的成像信息,通过toastmakemesh生成样品的体表面信息;再通过FDOT成像的实验步骤,得到样品的荧光图像、激光图像,结合CCD、样品、激光源的位置信息,以及体表面信息,可以重建得到荧光在样品中的分布图。FDOT重建算法可以主要调用toast++,小波变换,iso2mesh等开源程序包来完成整个重建算法,其中可以采用Galerkin FEM,zero-order Tikhonov regularization去处理采集到的稀疏荧光信息矩阵。After obtaining CT imaging, laser images, and fluorescence images, FDOT imaging can be reconstructed from CT imaging, laser images, and fluorescent images. Specifically, the body surface information of the sample can be obtained according to CT imaging; FDOT imaging is reconstructed according to the body surface information of the sample, the position information of the EMCCD, the sample and the laser, and the laser image and the fluorescence image. For example, firstly, 360-degree imaging information of the sample is obtained by CT imaging, and body surface information of the sample is generated by toastmakemesh; and the fluorescent image and laser image of the sample are obtained through the experimental steps of FDOT imaging, and the positions of the CCD, the sample, and the laser source are combined. Information, as well as body surface information, can be reconstructed to obtain a distribution of fluorescence in the sample. The FDOT reconstruction algorithm can mainly call open source packages such as toast++, wavelet transform, and iso2mesh to complete the entire reconstruction algorithm. Galerkin FEM and zero-order Tikhonov regularization can be used to process the collected sparse fluorescence information matrix.
综上所述,本发明实施例中,样品植入纳米材料,该纳米材料经X射线照射发出冷光,经激光照射发出荧光;X射线源向样品发射X射线,X射线平板探测器获得样品经X射线照射的CT成像,EMCCD获得样品经X射线照射的XLCT成像;激光器向样品发射激光,EMCCD获得样品经激光照射的激光图像和荧光图像;激光图像、荧光图像和CT成像用来重建FDOT成像,使FDOT成像系统与CT、XLCT成像系统相融合,可以在短时间内完成CT、XLCT和FDOT成像,缩短数据采集周期,并且可以弥补FDOT在深度信息上的不足,获得较为准确的深度信息,降低重建难度。 In summary, in the embodiment of the present invention, the sample is implanted into the nano material, and the nano material emits cold light by X-ray irradiation, and emits fluorescence by laser irradiation; the X-ray source emits X-rays to the sample, and the X-ray flat panel detector obtains the sample. CT imaging of X-ray irradiation, EMCCD obtains X-ray XLCT imaging of the sample; laser emits laser light to the sample, EMCCD obtains laser image and fluorescence image of the sample; laser image, fluorescence image and CT imaging are used to reconstruct FDOT imaging The FDOT imaging system can be combined with CT and XLCT imaging systems to complete CT, XLCT and FDOT imaging in a short time, shorten the data collection period, and can make up for the deficiencies of FDOT in depth information and obtain more accurate depth information. Reduce the difficulty of reconstruction.
本领域内的技术人员应明白,本发明的实施例可提供为方法、系统、或计算机程序产品。因此,本发明可采用完全硬件实施例、完全软件实施例、或结合软件和硬件方面的实施例的形式。而且,本发明可采用在一个或多个其中包含有计算机可用程序代码的计算机可用存储介质(包括但不限于磁盘存储器、CD-ROM、光学存储器等)上实施的计算机程序产品的形式。Those skilled in the art will appreciate that embodiments of the present invention can be provided as a method, system, or computer program product. Accordingly, the present invention may take the form of an entirely hardware embodiment, an entirely software embodiment, or a combination of software and hardware. Moreover, the invention can take the form of a computer program product embodied on one or more computer-usable storage media (including but not limited to disk storage, CD-ROM, optical storage, etc.) including computer usable program code.
本发明是参照根据本发明实施例的方法、设备(系统)、和计算机程序产品的流程图和/或方框图来描述的。应理解可由计算机程序指令实现流程图和/或方框图中的每一流程和/或方框、以及流程图和/或方框图中的流程和/或方框的结合。可提供这些计算机程序指令到通用计算机、专用计算机、嵌入式处理机或其他可编程数据处理设备的处理器以产生一个机器,使得通过计算机或其他可编程数据处理设备的处理器执行的指令产生用于实现在流程图一个流程或多个流程和/或方框图一个方框或多个方框中指定的功能的装置。The present invention has been described with reference to flowchart illustrations and/or block diagrams of methods, apparatus (system), and computer program products according to embodiments of the invention. It will be understood that each flow and/or block of the flowchart illustrations and/or FIG. These computer program instructions can be provided to a processor of a general purpose computer, special purpose computer, embedded processor, or other programmable data processing device to produce a machine for the execution of instructions for execution by a processor of a computer or other programmable data processing device. Means for implementing the functions specified in one or more of the flow or in a block or blocks of the flow chart.
这些计算机程序指令也可存储在能引导计算机或其他可编程数据处理设备以特定方式工作的计算机可读存储器中,使得存储在该计算机可读存储器中的指令产生包括指令装置的制造品,该指令装置实现在流程图一个流程或多个流程和/或方框图一个方框或多个方框中指定的功能。The computer program instructions can also be stored in a computer readable memory that can direct a computer or other programmable data processing device to operate in a particular manner, such that the instructions stored in the computer readable memory produce an article of manufacture comprising the instruction device. The apparatus implements the functions specified in one or more blocks of a flow or a flow and/or block diagram of the flowchart.
这些计算机程序指令也可装载到计算机或其他可编程数据处理设备上,使得在计算机或其他可编程设备上执行一系列操作步骤以产生计算机实现的处理,从而在计算机或其他可编程设备上执行的指令提供用于实现在流程图一个流程或多个流程和/或方框图一个方框或多个方框中指定的功能的步骤。These computer program instructions can also be loaded onto a computer or other programmable data processing device such that a series of operational steps are performed on a computer or other programmable device to produce computer-implemented processing for execution on a computer or other programmable device. The instructions provide steps for implementing the functions specified in one or more of the flow or in a block or blocks of a flow diagram.
以上所述的具体实施例,对本发明的目的、技术方案和有益效果进行了进一步详细说明,所应理解的是,以上所述仅为本发明的具体实施例而已,并不用于限定本发明的保护范围,凡在本发明的精神和原则之内,所做的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。 The above described specific embodiments of the present invention are further described in detail, and are intended to be illustrative of the embodiments of the present invention. All modifications, equivalent substitutions, improvements, etc., made within the spirit and scope of the invention are intended to be included within the scope of the invention.

Claims (10)

  1. 一种荧光散射光学断层成像系统,其特征在于,包括:A fluorescence scattering optical tomography system, comprising:
    载物台,用于承载样品,所述样品被植入纳米材料,所述纳米材料经X射线照射发出冷光,经激光照射发出荧光;a stage for carrying a sample, the sample being implanted with a nano material, the nano material emitting cold light by X-ray irradiation, and emitting fluorescence by laser irradiation;
    X射线源,用于向所述载物台上的样品发射X射线;An X-ray source for emitting X-rays to a sample on the stage;
    X射线平板探测器,用于获得所述样品经X射线照射的CT成像;An X-ray flat panel detector for obtaining CT imaging of the sample by X-ray irradiation;
    EMCCD,用于获得所述样品经X射线照射的XLCT成像;EMCCD for obtaining XLCT imaging of the sample by X-ray irradiation;
    激光器,用于向所述样品发射激光;a laser for emitting laser light to the sample;
    所述EMCCD还用于获得所述样品经激光照射的激光图像和荧光图像,所述激光图像、荧光图像和CT成像用于重建FDOT成像。The EMCCD is also used to obtain laser-irradiated laser images and fluorescent images of the sample, the laser images, fluorescent images, and CT imaging for reconstructing FDOT imaging.
  2. 如权利要求1所述的荧光散射光学断层成像系统,其特征在于,所述载物台为旋转载物台;所述X射线平板探测器具体用于获得所述样品在旋转载物台旋转的多个角度的CT成像;所述EMCCD具体用于获得所述样品在旋转载物台旋转的多个角度的XLCT成像。A fluorescence scattering optical tomography system according to claim 1, wherein said stage is a rotating stage; said X-ray flat panel detector is specifically for obtaining rotation of said sample on a rotating stage CT imaging at multiple angles; the EMCCD is specifically used to obtain XLCT imaging of multiple angles of rotation of the sample on a rotating stage.
  3. 如权利要求1所述的荧光散射光学断层成像系统,其特征在于,还包括:The fluorescence scattering optical tomography system of claim 1 further comprising:
    微位移台,用于通过夹持激光器的光纤头来控制激光移动;所述EMCCD具体用于获得所述样品经移动的激光照射的多个激光图像和荧光图像。A micro-displacement stage for controlling laser movement by clamping a fiber optic head of the laser; the EMCCD is specifically for obtaining a plurality of laser images and fluorescent images of the sample irradiated by the moving laser.
  4. 如权利要求1所述的荧光散射光学断层成像系统,其特征在于,还包括:The fluorescence scattering optical tomography system of claim 1 further comprising:
    设于EMCCD与载物台之间的滤光片,用于滤除所述样品经激光照射发出的荧光,使EMCCD获得所述样品经激光照射的激光图像;滤除所述激光器发出的激光,使EMCCD获得所述样品经激光照射的荧光图像。a filter disposed between the EMCCD and the stage for filtering the fluorescence emitted by the sample by laser irradiation, so that the EMCCD obtains a laser image of the sample irradiated by the laser; filtering the laser emitted by the laser, The EMCCD was subjected to a laser-irradiated fluorescence image of the sample.
  5. 一种荧光散射光学断层成像方法,其特征在于,包括:A fluorescence scattering optical tomography method, comprising:
    在载物台上放置样品,所述样品被植入纳米材料,所述纳米材料经X射线照射发出冷光,经激光照射发出荧光;Placing a sample on a stage, the sample being implanted with a nano material that emits luminescence by X-ray irradiation and emits fluorescence by laser irradiation;
    打开X射线源及X射线平板探测器,X射线源向所述载物台上的样品发射X射线,X射线平板探测器获得所述样品经X射线照射的CT成像;EMCCD获得所述样品经X射线照射的XLCT成像;Opening an X-ray source and an X-ray flat panel detector, the X-ray source emitting X-rays to the sample on the stage, and the X-ray flat panel detector obtains CT imaging of the sample by X-ray irradiation; the EMCCD obtains the sample by X-ray irradiation of XLCT imaging;
    关闭X射线源及X射线平板探测器,打开激光器,激光器向所述样品发射激光;EMCCD获得所述样品经激光照射的激光图像和荧光图像;Turning off the X-ray source and the X-ray flat panel detector, turning on the laser, and the laser emitting laser light to the sample; the EMCCD obtains the laser image and the fluorescent image of the sample irradiated by the laser;
    根据所述CT成像、激光图像和荧光图像,重建得到FDOT成像。 According to the CT imaging, the laser image, and the fluorescence image, FDOT imaging is reconstructed.
  6. 如权利要求5所述的方法,其特征在于,所述载物台为旋转载物台;所述样品在旋转载物台上旋转;The method of claim 5 wherein said stage is a rotating stage; said sample is rotated on a rotating stage;
    X射线平板探测器获得所述样品经X射线照射的CT成像,包括:X射线平板探测器获得所述样品在旋转载物台旋转的多个角度的CT成像;An X-ray flat panel detector obtains CT imaging of the sample by X-ray irradiation, comprising: an X-ray flat panel detector obtaining CT images of the plurality of angles of rotation of the sample on the rotating stage;
    EMCCD获得所述样品经X射线照射的XLCT成像,包括:EMCCD获得所述样品在旋转载物台旋转的多个角度的XLCT成像。The EMCCD obtains X-ray illuminated XLCT imaging of the sample, including: EMCCD obtains multiple angles of XLCT imaging of the sample rotating on a rotating stage.
  7. 如权利要求5所述的方法,其特征在于,EMCCD获得所述样品经X射线照射的XLCT成像,包括:The method of claim 5 wherein the EMCCD obtains X-ray illuminated XLCT imaging of the sample, comprising:
    通过有限元方法解散射方程
    Figure PCTCN2016087425-appb-100001
    得到矩阵方程M·φ(r)=F·ε·X(r)·ρ,再通过稀疏矩阵归一化法解
    Figure PCTCN2016087425-appb-100002
    最小化问题,得到ρ;根据ρ重建XLCT成像;
    Solving the scattering equation by finite element method
    Figure PCTCN2016087425-appb-100001
    Obtain the matrix equation M·φ(r)=F·ε·X(r)·ρ, and then solve it by sparse matrix normalization method.
    Figure PCTCN2016087425-appb-100002
    Minimize the problem, get ρ; reconstruct XLCT imaging according to ρ;
    其中,r是位置;D(r)是扩散系数,D(r)=(3(μa(r)+(1-g)μs(r)))-1;μa(r)是吸收系数;μs(r)是散射系数;g是各项异性参数;φ(r)是荧光强度;S(r)是光源;Where r is the position; D(r) is the diffusion coefficient, D(r) = (3(μ a (r) + (1 - g) μ s (r))) -1 ; μ a (r) is the absorption Coefficient; μ s (r) is the scattering coefficient; g is the anisotropic parameter; φ(r) is the fluorescence intensity; S(r) is the light source;
    M是光子密度;F是光发散的扩散系数;ε是光学视野;X(r)是X射线强度;ρ是光发散的吸收系数;M is the photon density; F is the diffusion coefficient of light divergence; ε is the optical field of view; X(r) is the X-ray intensity; ρ is the absorption coefficient of light divergence;
    A=(M-1F)·ε·X(r);Φ=A·ρ;λ是归一性参数。A = (M - 1 F) · ε · X (r); Φ = A · ρ; λ is a normalized parameter.
  8. 如权利要求5所述的方法,其特征在于,进一步包括:微位移台通过夹持激光器的光纤头来控制激光移动;The method of claim 5, further comprising: the micro-displacement stage controls laser movement by clamping a fiber optic head of the laser;
    EMCCD获得所述样品经激光照射的激光图像和荧光图像,包括:EMCCD获得所述样品经移动的激光照射的多个激光图像和荧光图像。The EMCCD obtains a laser-irradiated laser image and a fluorescent image of the sample, including: EMCCD obtains a plurality of laser images and fluorescent images of the sample irradiated by the moving laser.
  9. 如权利要求5所述的方法,其特征在于,EMCCD获得所述样品经激光照射的激光图像和荧光图像,包括:The method of claim 5 wherein the EMCCD obtains laser-irradiated laser images and fluorescent images of said sample, comprising:
    在EMCCD与载物台之间放置滤光片,滤除所述样品经激光照射发出的荧光,EMCCD获得所述样品经激光照射的激光图像;A filter is placed between the EMCCD and the stage to filter out the fluorescence emitted by the sample by laser irradiation, and the EMCCD obtains a laser image of the sample irradiated by the laser;
    更换滤光片,滤除所述激光器发出的激光,EMCCD获得所述样品经激光照射的荧光图像。The filter is replaced, the laser light emitted by the laser is filtered out, and the EMCCD obtains a fluorescent image of the sample irradiated with laser light.
  10. 如权利要求9所述的方法,其特征在于,根据所述CT成像、激光图像和荧光图像,重建得到FDOT成像,包括:The method of claim 9 wherein reconstructing the FDOT image based on the CT imaging, the laser image, and the fluorescence image comprises:
    根据所述CT成像得到所述样品的体表面信息; Obtaining body surface information of the sample according to the CT imaging;
    根据所述样品的体表面信息,所述EMCCD、样品和激光器的位置信息,以及所述激光图像和荧光图像,重建得到FDOT成像。 The FDOT imaging is reconstructed based on the body surface information of the sample, the position information of the EMCCD, the sample and the laser, and the laser image and the fluorescence image.
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