WO2018000186A1 - Système et procédé de tomographie optique à diffusion de fluorescence - Google Patents

Système et procédé de tomographie optique à diffusion de fluorescence Download PDF

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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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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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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00—Apparatus for radiation diagnosis, e.g. combined with radiation therapy equipment
    • A61B6/02—Devices for diagnosis sequentially in different planes; Stereoscopic radiation diagnosis
    • A61B6/03—Computerised 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.

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Abstract

La présente invention concerne un système de tomographie optique à diffusion de fluorescence et un procédé. Le système comprend une platine pour supporter un spécimen implanté avec un nanomatériau émettant de la lumière froide par irradiation aux rayons X, et émettant une fluorescence par irradiation laser ; une source de rayons X pour émettre des rayons X sur l'échantillon situé sur la platine ; un détecteur de plaque à rayons X pour acquérir l'imagerie par tomodensitométrie du spécimen par irradiation aux rayons X ; un capteur EMCCD pour l'acquisition de l'imagerie XLCT du spécimen par irradiation aux rayons X ; et un laser pour l'émission de lumière laser sur l'échantillon, où l'EMCCD est également utilisé pour acquérir l'image laser et l'image fluorescente du spécimen irradié par la lumière laser, et l'image laser, l'image de fluorescence et l'imagerie par tomodensitométrie sont utilisées pour reconstruire l'imagerie FDOT. Le système et le procédé d'imagerie peuvent être utilisés pour obtenir des informations de profondeur plus précise, réduire la difficulté de reconstruction et raccourcir le cycle d'acquisition de données.
PCT/CN2016/087425 2016-06-28 2016-06-28 Système et procédé de tomographie optique à diffusion de fluorescence WO2018000186A1 (fr)

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Publication number Priority date Publication date Assignee Title
CN109646032A (zh) * 2018-11-14 2019-04-19 天津大学 一种基于加权调制的多光束x射线激发发光断层成像方法
CN109646032B (zh) * 2018-11-14 2022-06-10 天津大学 一种基于加权调制的多光束x射线激发发光断层成像方法
CN110731759A (zh) * 2019-11-25 2020-01-31 窦少彬 一种多模式3d荧光断层动物分子影像扫描设备

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