WO2019015436A1 - Dispositif d'endo-microscopie tomographique - Google Patents

Dispositif d'endo-microscopie tomographique Download PDF

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Publication number
WO2019015436A1
WO2019015436A1 PCT/CN2018/091977 CN2018091977W WO2019015436A1 WO 2019015436 A1 WO2019015436 A1 WO 2019015436A1 CN 2018091977 W CN2018091977 W CN 2018091977W WO 2019015436 A1 WO2019015436 A1 WO 2019015436A1
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WO
WIPO (PCT)
Prior art keywords
light
unit
area array
sample
imaging
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PCT/CN2018/091977
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English (en)
Chinese (zh)
Inventor
王强
邵金华
孙锦
段后利
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苏州微景医学科技有限公司
南京亘瑞医疗科技有限公司
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Publication of WO2019015436A1 publication Critical patent/WO2019015436A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/00131—Accessories for endoscopes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/00163—Optical arrangements
    • A61B1/00165—Optical arrangements with light-conductive means, e.g. fibre optics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/00163—Optical arrangements
    • A61B1/00186—Optical arrangements with imaging filters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B1/00—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor
    • A61B1/04—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances
    • A61B1/043—Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopes; Illuminating arrangements therefor combined with photographic or television appliances for fluorescence imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0033—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • A61B5/0084—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes for introduction into the body, e.g. by catheters

Definitions

  • the present invention relates to the field of medical devices, and more particularly to a tomographic endoscopic microscopic imaging device.
  • Tumors are major diseases that pose a serious threat to human health.
  • the number of cancers (malignant tumors) worldwide has increased at an average annual rate of 3% to 5%. Cancer has become one of the most important causes of death in humans.
  • clinical studies have found that early tumors are not associated with metastasis and are easily resected. Therefore, early detection and early diagnosis of tumors are the key to improving the level of tumor treatment, reducing the cost of treatment, and improving the quality of life after treatment. Numerous studies have shown that more than 90% of tumors are derived from epithelial cell lesions, and molecular and cellular levels of variation occur during cancer development.
  • Fiber-optic beam-based high-resolution optical endoscopic imaging technology that achieves micron or sub-micron resolution, enabling endoscopic magnification up to 1000 times, and is lossless compared to other medical imaging techniques (such as CT, MRI, PET, etc.)
  • Real-time, in-vivo detection of micro-neoplastic lesions and other technical advantages can better improve the early diagnosis rate of tumors.
  • the probe end of the endoscopic imaging can be deeply penetrated into the living body to complete the real-time non-destructive testing of the micro-scale in vivo, and realize the “in-vivo biopsy” without sampling, which brings new technical means for early detection of molecular molecular lesions.
  • the present invention has been made in consideration of the above problems.
  • the present invention provides a tomographic endoscopic microscopic imaging apparatus comprising a light emitting unit, a structured light unit, a steering unit and an area array detecting unit, wherein the light emitting unit is for emitting a light beam; the structured light unit is for Converting the beam into structured light; the steering unit is for diverting the structured light and transmitting fluorescence of the sample; and the area array detecting unit is configured to acquire the fluorescence.
  • the light emitting unit includes: a light source for emitting a collimated beam; and a beam expanding assembly disposed at an exit of the light source for expanding the collimated beam.
  • the beam expanding assembly includes a narrow band filter and a beam expander disposed in sequence, wherein the narrow band filter is used to filter the collimated beam; the beam expander is used for filtering after filtering The beam is expanded.
  • the steering unit is a dichroic mirror.
  • the structured light unit comprises: a digital micromirror device; or a spatial light modulator; or a grating and a driver that controls the movement of the grating.
  • the apparatus further includes an endoscopic unit disposed downstream of the steering unit, the endoscope unit for conducting and focusing the diverted beam onto the sample and receiving fluorescence emitted by the sample; The steering unit is then collected by the area array detecting unit.
  • the endoscopic unit includes a coupling objective lens and an imaging fiber bundle, wherein the coupling objective lens is disposed at one end of the imaging ray bundle for coupling the focused beam into a proximal end of the fiber bundle; And the imaging fiber bundle is used to conduct an incoming beam.
  • the endoscopic unit further includes a micro objective lens disposed at the other end of the imaging ray bundle for focusing a beam of light conducted by the bundle of fibers onto the sample.
  • the area array detection unit includes a focus lens and an area array detector disposed in sequence, wherein the focus lens is used to focus fluorescence emitted by the sample; the area array detector is used to acquire a fluorescent signal.
  • the area array detecting unit further includes a long pass filter disposed between the focus lens and the area array detector for filtering out stray light.
  • the tomographic endoscopic microscopic imaging device uses a surface light source to excite the sample, and uses the area array detecting unit to detect the sample excitation light, which can greatly improve the imaging speed of the tissue molecules and realize real-time imaging.
  • the use of structured light units in a tomographic microscopy imaging apparatus solves the problem of image blur caused by the interference of the wide-field imaging itself due to the background light of the upper and lower layers of the focus plane.
  • FIG. 1 shows a schematic block diagram of a tomographic endoscopic microscopic imaging apparatus in accordance with one embodiment of the present invention
  • FIG. 2 shows a schematic diagram of an optical path of a tomographic endoscopic microscopic imaging device in accordance with one embodiment of the present invention.
  • the tomographic microscopic imaging apparatus 100 includes a light emitting unit 110, a structured light unit 150, a steering unit 120, and an area array detecting unit 140.
  • the tomographic endoscopic microscopic imaging device 100 can be widely applied to tissue molecular imaging of various parts such as the digestive tract and the respiratory tract to realize early diagnosis of the tumor.
  • the light emitting unit 110 is for emitting a light beam.
  • light emitting unit 110 can include a light source 112 and a beam expanding assembly 114.
  • Light source 112 is used to emit a collimated beam of light.
  • Light source 112 can be a laser that emits a collimated laser of a particular wavelength. The specific wavelength range may be from 20 nm to 2000 nm. Lasers in this wavelength range can excite a wide range of phosphors.
  • Light source 112 can be a quantum well laser, a solid state laser, a gas laser (eg, an argon ion laser), or a laser diode.
  • a beam expander assembly 114 is disposed at the exit of the light source 112 for expanding the collimated beam of light from the source 112.
  • the beam expanding assembly 114 can include a narrow band filter (not shown) and a beam expander disposed in sequence.
  • a narrow band filter is used to filter the collimated beam from source 112.
  • the narrowband filter filters out light of the desired wavelength, for example, allowing light from 500 nm to 600 nm to pass through the narrowband filter for exciting a wide range of fluorescence.
  • the beam expander can include two beam expanding lenses L1, L2 that cooperate to expand the beam passing through the narrow band filter to change the diameter of the collimated beam.
  • the structured light unit 150 is used to convert the light beam emitted by the light emitting unit 110 into structured light, and various embodiments of the structured light unit 150 will be described in detail later.
  • the diverting unit 120 is located downstream of the structured light unit 150 for steering structured light formed by the structured light unit 150 and capable of transmitting fluorescence of the sample.
  • the solid line is used to indicate the light beam emitted by the light emitting unit 110
  • the broken line is used to indicate the fluorescence of the sample being excited.
  • the steering unit 120 is used to separate the structured light generated by the structured light unit 150 and the fluorescence generated by the sample excitation.
  • the transmittance of the diverting unit 120 to the fluorescence can be more than 90%, while substantially all of the light of the other wavelengths is reflected. Then, the structured light generated by the structured light unit 150 is reflected to the endoscopic unit 130 as it passes through the steering unit 120.
  • the steering unit 120 that satisfies the above conditions may be a dichroic mirror.
  • the dichroic mirror may have a wavelength in the wavelength range of 40 nm to 2200 nm.
  • the tomographic microscopy imaging apparatus 100 further includes an endoscopic unit 130 disposed downstream of the steering unit 120.
  • the endoscope unit 130 is configured to conduct and focus the light beam that is turned by the steering unit 120 onto the sample, and receive the fluorescence emitted by the sample. The fluorescence is collected by the area array detecting unit 140 via the steering unit 120.
  • the endoscopic unit 130 can include a coupling objective 132, a miniature objective 136, and an imaging fiber bundle 134 coupled between the coupling objective 132 and the micro objective 136.
  • the coupling objective 132 is used to couple (e.g., focus) the beam into the proximal end of the imaging fiber bundle 134 (near the operator's end).
  • the imaging fiber bundle 134 is used to conduct a beam of light to the distal end of the imaging fiber bundle 134 (away from the end of the operator).
  • the miniature objective lens 136 is used to focus the laser light conducted by the imaging fiber bundle 134 onto the detection surface of the sample.
  • the detection surface can be located at a desired depth below the surface of the sample.
  • the fluorophore at the detection face of the sample is excited to fluoresce.
  • the fluorescent signal is collected by the miniature objective lens 136, conducted through the imaging fiber bundle 134 and the coupling objective 132, and passes through the steering unit 120 into the area array detecting unit 140.
  • the number of bundles of light included in the imaging fiber bundle 134 can be greater than ten.
  • the miniature objective lens 136 is not required.
  • the area array detecting unit 140 collects fluorescence that is sequentially returned through the endoscope unit 130 and the steering unit 120.
  • the area array detection unit 140 includes a focus lens 142 and an area array detector 146.
  • a focusing lens 142 is used to focus the fluorescence emitted by the sample.
  • the focused fluorescence is sensitized on the photosensitive surface of the area array detector 146.
  • the area array detector 146 may be various types of area array cameras such as a CCD (Charge Coupled Element) area array camera or a CMOS (Complementary Metal Oxide Semiconductor) area array camera.
  • the imaging speed of the area array detector 146 is in the range of several tens of frames to tens of millions of frames.
  • the area array detecting unit 140 can form a complete image each time, that is, the imaging speed of the tomographic microscopy imaging device is the imaging speed of the area array detecting unit 140, and the observable tissue molecular image can be quickly realized.
  • the area array detecting unit 140 further includes a long pass filter.
  • a long pass filter (not shown) is disposed between the focus lens 142 and the area array detector 146 for filtering out stray light.
  • the collimated beam emitted by the light source 112 is expanded by the beam expanding component 114, converted into structured light by the structured light unit 150, and the steering unit 120 folds the structured light into the endoscope unit 130, and the endoscope unit 130
  • the beam is conducted to the sample, excites fluorescence and is transmitted back to the area array detection unit 140 for imaging.
  • the data collected by the area array detector can be sent to a computer for receipt and processing by the computer.
  • the computer can also control the exposure and gain of the structured light unit, the area array detector, and the transmission power of the light emitting unit.
  • the structured light unit 150 is disposed between the light emitting unit 110 and the steering unit 120 for converting the light beam emitted from the light emitting unit 110 into structured light.
  • the structured light belongs to the characterized beam.
  • the structured light unit 150 achieves the purpose of light wave modulation by modulating the phase of the light.
  • structured light unit 150 can include a grating and a driver (eg, a motor) that controls the movement of the grating.
  • the grating can be a cosine grating.
  • the light beam emitted by the light emitting unit 110 is projected onto the sample through the grating to form structured light illumination.
  • each movement of 1/3 of the grating period corresponds to a phase shift of the grating pattern of 2 ⁇ /3.
  • the exposure speed of the area array detecting unit 140 is synchronized with the movement of the grating.
  • the grating may be a grating of greater than or equal to 10 line pairs per mm, such as 10 line pairs/mm, 20 line pairs/mm, 30 line pairs/mm or 40 line pairs/mm.
  • the structured light unit 150 can also employ a spatial light modulator.
  • the spatial light modulator can modulate the phase of the light for active light modulation under active control. It can easily load information into one-dimensional or two-dimensional light field, and utilize the advantages of wide bandwidth of light and multi-channel parallel processing to quickly process the loaded information.
  • the structured light unit 150 can also utilize various existing digital micromirror devices (DMDs).
  • DMD is an electronic input, optical output micro-electromechanical system (MEMS) that controls the flipping of internal array elements through electronic inputs to form the desired grating, allowing operators to perform high-speed, efficient and reliable Spatial light modulation.
  • MEMS micro-electromechanical system
  • the disclosed apparatus and method may be implemented in other manners.
  • the device embodiments described above are merely illustrative.
  • the division of the unit is only a logical function division.
  • there may be another division manner for example, multiple units or components may be combined or Can be integrated into another device, or some features can be ignored or not executed.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Surgery (AREA)
  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Optics & Photonics (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)

Abstract

La présente invention concerne un dispositif d'endo-microscopie tomographique (100) comprenant une unité de transmission de lumière (110), une unité de structuration de lumière (150), une unité de déviation (120) et une unité de détection de réseau plan (140). La source de transmission de lumière (110) permet d'émettre un faisceau lumineux. L'unité de structuration de lumière (150) permet de convertir le faisceau lumineux en lumière structurée. L'unité de déviation (120) permet de dévier la lumière structurée et permet à la lumière fluorescente émise par un échantillon de la traverser. L'unité de détection de réseau plan (140) permet de collecter la lumière fluorescente. Le dispositif d'endo-microscopie tomographique (100) utilise une source de lumière plane pour exciter un échantillon, et utilise une unité de détection de réseau plan (140) pour détecter la lumière excitée de l'échantillon, ce qui permet d'augmenter de façon significative la vitesse d'imagerie d'une molécule de tissu, et de réaliser une imagerie en temps réel. De plus, le dispositif d'endo-microscopie tomographique (100) utilise une unité de structuration de lumière (150) pour résoudre le problème de production d'une image floue par une imagerie de champ large en raison de l'interférence de la lumière de fond au-dessus et au-dessous d'un plan focal.
PCT/CN2018/091977 2017-07-20 2018-06-20 Dispositif d'endo-microscopie tomographique WO2019015436A1 (fr)

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CN201710597045.5A CN107361724A (zh) 2017-07-20 2017-07-20 层析内窥显微成像装置

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CN107361724A (zh) * 2017-07-20 2017-11-21 南京亘瑞医疗科技有限公司 层析内窥显微成像装置
CN107361723B (zh) * 2017-07-20 2024-02-13 无锡海斯凯尔医学技术有限公司 快速组织分子光谱成像装置

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CN202069570U (zh) * 2010-12-09 2011-12-14 深圳大学 一种荧光内窥成像系统
CN103926228A (zh) * 2014-04-28 2014-07-16 江苏天宁光子科技有限公司 一种激光扫描共焦荧光显微内窥成像系统
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