WO2019015436A1

WO2019015436A1 - Tomographic endo-microscopy device

Info

Publication number: WO2019015436A1
Application number: PCT/CN2018/091977
Authority: WO
Inventors: 王强; 邵金华; 孙锦; 段后利
Original assignee: 苏州微景医学科技有限公司; 南京亘瑞医疗科技有限公司
Priority date: 2017-07-20
Filing date: 2018-06-20
Publication date: 2019-01-24
Also published as: CN107361724A

Abstract

A tomographic endo-microscopy device (100) comprises a light transmitting unit (110), a light-structuring unit (150), a diversion unit (120), and a planar array detecting unit (140). The light transmitting unit (110) is used to transmit a light beam. The light-structuring unit (150) is used to convert the light beam into structured light. The diversion unit (120) is used to divert the structured light and allows fluorescent light emitted by a sample to pass therethrough. The planar array detecting unit (140) is used to collect the fluorescent light. The tomographic endo-microscopy device (100) adopts a planar light source to excite a sample, and uses a planar array detecting unit (140) to detect the excited light of the sample, thereby significantly increasing a speed of imaging a tissue molecule, and realizing real-time imaging. Moreover, the tomographic endo-microscopy device (100) uses a light-structuring unit (150) to solve a problem in which wide field imaging produces a blurry image due to interference of background light above and below a focal plane.

Description

Chromatographic endoscopic microscopic imaging device

Technical field

The present invention relates to the field of medical devices, and more particularly to a tomographic endoscopic microscopic imaging device.

Background technique

Tumors are major diseases that pose a serious threat to human health. In the past three decades, 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. At present, 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.

Summary of the invention

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.

Illustratively, 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.

Illustratively, 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.

Illustratively, the steering unit is a dichroic mirror.

Illustratively, 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.

Illustratively, 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.

Illustratively, 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.

Illustratively, 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.

Illustratively, 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.

Illustratively, 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. In addition, 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.

DRAWINGS

The above as well as other objects, features and advantages of the present invention will become more apparent from the embodiments of the invention. The drawings are intended to provide a further understanding of the embodiments of the invention, In the figures, the same reference numerals generally refer to the same or similar parts or steps.

1 shows a schematic block diagram of a tomographic endoscopic microscopic imaging apparatus in accordance with one embodiment of the present invention;

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.

Detailed ways

In order to make the objects, the technical solutions and the advantages of the present invention more apparent, the exemplary embodiments according to the present invention will be described in detail below with reference to the accompanying drawings. It is apparent that the described embodiments are only a part of the embodiments of the present invention, and are not to be construed as limiting the embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention described herein without departing from the scope of the invention are intended to fall within the scope of the invention.

1 and 2 schematically illustrate a block diagram and an optical path diagram, respectively, of a tomographic endoscopic microscopic imaging apparatus 100 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. In one embodiment, 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. In a preferred embodiment, 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. In Figs. 1 and 2, the solid line is used to indicate the light beam emitted by the light emitting unit 110, and 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. Fluorescence returned along the same optical path as the beam is transmitted almost entirely through the steering unit 120 and conducted to the area array detecting unit 140. The steering unit 120 that satisfies the above conditions may be a dichroic mirror. Preferably, 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. In a preferred embodiment, as shown in FIG. 2, 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.

On the probe light path, the area array detecting unit 140 collects fluorescence that is sequentially returned through the endoscope unit 130 and the steering unit 120. In a preferred embodiment, 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. Optionally, 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.

In summary, 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.

Illustratively, the data collected by the area array detector can be sent to a computer for receipt and processing by the computer. In addition, 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.

In a preferred embodiment, 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. When three source images are formed for each cycle (ie, the grating movement period), each movement of 1/3 of the grating period corresponds to a phase shift of the grating pattern of 2π/3. At the same time, the exposure speed of the area array detecting unit 140 is synchronized with the movement of the grating. Three phase shifts (0, 2π/3, 4π/3) were used to obtain three source images of the sample, and then a tomographic image of the sample was obtained by structured light reconstruction. For example, if the desired frame rate is 10 frames per second, the raster needs to be moved 30 times per second to form 30 source images. In addition, the grating can also be moved 6 times or 9 times in one cycle, and correspondingly, 1/6 or 1/9 of the phase shift grating period. The "structured light reconstruction" algorithm may be various algorithms that may be present or may occur in the future. Since structural light reconstruction is not an inventive point of the present invention, the present invention is not described in further detail. 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.

In another preferred embodiment, 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.

In still another preferred embodiment, 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.

The use of structured light reconstruction techniques in tomographic microscopy imaging devices 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 planes of the focus plane.

Although the example embodiments have been described herein with reference to the drawings, it is understood that the foregoing exemplary embodiments are merely illustrative and are not intended to limit the scope of the invention. A person skilled in the art can make various changes and modifications without departing from the scope and spirit of the invention. All such changes and modifications are intended to be included within the scope of the present invention as claimed.

In the several embodiments provided by the present application, it should be understood that the disclosed apparatus and method may be implemented in other manners. For example, the device embodiments described above are merely illustrative. For example, the division of the unit is only a logical function division. In actual implementation, 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.

In the description provided herein, numerous specific details are set forth. However, it is understood that the embodiments of the invention may be practiced without these specific details. In some instances, well-known methods, structures, and techniques are not shown in detail so as not to obscure the understanding of the description.

Similarly, the various features of the present invention are sometimes grouped together into a single embodiment, figure, in the description of exemplary embodiments of the invention, in the description of the exemplary embodiments of the invention. Or in the description of it. However, the method of the present invention should not be construed as reflecting the intention that the claimed invention requires more features than those specifically recited in the appended claims. Rather, as the invention is reflected by the appended claims, it is claimed that the technical problems can be solved with fewer features than all of the features of a single disclosed embodiment. Therefore, the claims following the specific embodiments are hereby explicitly incorporated into the embodiments, and each of the claims as a separate embodiment of the invention.

It will be understood by those skilled in the art that all features disclosed in the specification, including the accompanying claims, the abstract and the drawings, and all methods or devices so disclosed, may be employed in any combination, unless the features are mutually exclusive. Process or unit combination. Each feature disclosed in this specification (including the accompanying claims, the abstract and the drawings) may be replaced by alternative features that provide the same, equivalent or similar purpose.

Moreover, those skilled in the art will appreciate that, although some embodiments described herein include certain features that are not included in other embodiments, and other features, combinations of features of different embodiments are intended to be within the scope of the present invention. Different embodiments are formed and formed. For example, in the claims, any one of the claimed embodiments can be used in any combination.

It is to be noted that the above-described embodiments are illustrative of the invention and are not intended to be limiting, and that the invention may be devised without departing from the scope of the appended claims. In the claims, any reference signs placed between parentheses shall not be construed as a limitation. The word "comprising" does not exclude the presence of the elements or steps that are not recited in the claims. The word "a" or "an" The invention can be implemented by means of hardware comprising several distinct elements and by means of a suitably programmed computer. In the unit claims enumerating several means, several of these means can be embodied by the same hardware item. The use of the words first, second, and third does not indicate any order. These words can be interpreted as names.

The above is only the specific embodiment of the present invention or the description of the specific embodiments, and the scope of the present invention is not limited thereto, and any person skilled in the art can easily within the technical scope disclosed by the present invention. Any changes or substitutions are contemplated as being within the scope of the invention. The scope of the invention should be determined by the scope of the claims.

Claims

A tomographic endoscopic microscopic imaging device comprising a light emitting unit, a structured light unit, a steering unit and an area array detecting unit, wherein

The light emitting unit is configured to emit a light beam;

The structured light unit is configured to convert the light beam into structured light;

The steering unit is configured to divert the structured light and transmit fluorescence of the sample;

The area array detecting unit is configured to collect the fluorescence.
The apparatus of claim 1 wherein said light emitting unit comprises:

a light source for emitting a collimated beam;

A beam expander assembly is disposed at the exit of the light source for expanding the collimated beam.
The apparatus according to claim 2, wherein said beam expanding assembly comprises a narrow band filter and a beam expander arranged in sequence, wherein

The narrow band filter is configured to filter the collimated beam;

The beam expander is used to expand the filtered light beam.
The apparatus of claim 1 wherein said steering unit is a dichroic mirror.
The apparatus of claim 1 wherein said structured light unit comprises:

Digital micromirror device; or

Spatial light modulator; or

A grating and a driver that controls the movement of the grating.
The apparatus of claim 1 wherein said apparatus further comprises an endoscopic unit disposed downstream of said steering unit, said endoscopic unit for conducting and focusing the diverted beam onto the sample and receiving the sample Fluorescence; the fluorescence is collected by the area array detecting unit after the steering unit.
The apparatus of claim 6 wherein said endoscopic unit comprises a coupling objective and an imaging fiber bundle, wherein

The coupling objective is disposed at one end of the imaging ray bundle for coupling the focused beam into a proximal end of the bundle;

The imaging fiber bundle is used to conduct an incoming beam.
The apparatus according to claim 7, wherein said endoscopic unit further comprises a micro objective lens disposed at the other end of said image beam of light for focusing said beam of light guided by said bundle of fibers On the sample.
The apparatus according to claim 1, wherein said area array detecting unit comprises a focus lens and an area array detector which are sequentially disposed, wherein

The focusing lens is configured to focus fluorescence emitted by the sample;

The area array detector is used to collect fluorescent signals.
The apparatus according to claim 1, wherein said area array detecting unit further comprises a long pass filter, said long pass filter being disposed between said focus lens and said area array detector for Filter out stray light.