CN107361725B - Quick tissue molecule imaging device - Google Patents
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Classifications
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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
- 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
- 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
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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
- A61B1/04—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
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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
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
- A61B5/0062—Arrangements for scanning
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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
- 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
Abstract
The embodiment of the invention provides a rapid tissue molecule imaging device, which comprises a light emitting unit, a steering unit, a scanning unit and a linear array detection unit, wherein the light emitting unit is used for emitting a ray beam; the steering unit is used for steering the linear light beam and transmitting fluorescence of the sample; the scanning unit is used for adjusting the direction of the turned linear light beam to scan the sample line by line; and the linear array detection unit is used for collecting the fluorescence. The rapid tissue molecule imaging device adopts a linear light source to excite a sample, adopts a one-dimensional scanning unit to scan a linear light beam, and adopts a linear array detection unit to detect excitation light of the sample so as to realize confocal in one-dimensional direction. The linear beam and the linear array detection unit are combined to image tissue molecules, so that the imaging speed of the tissue molecules can be greatly improved, real-time imaging can be realized, and the scanning unit only performs one-dimensional scanning, so that the stability of the system can be effectively improved.
Description
Technical Field
The invention relates to the field of medical instruments, in particular to a rapid tissue molecular imaging device.
Background
Tumors are serious diseases that severely threaten human health. Numerous studies have shown that more than 90% of tumors originate from epithelial lesions and that variations at the molecular and cellular levels occur during the course of cancer development. The high-resolution optical endoscopic imaging technology based on the optical fiber bundles can achieve the resolution of micrometers or submicron, enables the amplification factor of an endoscope to reach 1000 times, has the technical advantages of no damage, real-time detection of micro-tumor lesions in real time and the like compared with other medical imaging technologies (such as CT, MRI, PET and the like), and can better improve the early diagnosis rate of tumors. The probe end of the endoscopic imaging can go deep into the living body to finish the micron-sized in-vivo real-time nondestructive detection, realize the in-vivo biopsy without sampling, and bring new technical means for early cell molecular lesion detection.
Disclosure of Invention
The present invention has been made in view of the above-described problems. The invention provides a rapid tissue molecular imaging device, which comprises a light emitting unit, a steering unit, a scanning unit, an endoscopic unit and a linear array detection unit, wherein the light emitting unit comprises a light source and a beam expanding line focus device, the light source is used for emitting collimated light beams, the beam expanding line focus device is arranged at an outlet of the light source and comprises a beam expanding lens and a cylindrical lens, the beam expanding lens is used for expanding the collimated light beams emitted by the light source so as to change the diameter of the collimated light beams, and the cylindrical lens is used for focusing the light beams subjected to beam expansion into linear light beams in one dimension; the steering unit is used for steering the linear light beam and transmitting fluorescence of the sample; the scanning unit is used for adjusting the direction of the turned linear light beam to scan the sample line by line; the endoscope unit is used for conducting and focusing the focused line light beam onto a sample and receiving fluorescence emitted by the sample, and comprises a coupling objective lens and an imaging optical fiber beam, wherein the coupling objective lens is arranged at one end of the imaging optical fiber beam and is used for coupling the focused line light beam into the proximal end of the imaging optical fiber beam, and the imaging optical fiber beam is used for conducting the incoming line light beam; and the linear array detection unit is used for collecting the fluorescence.
Illustratively, the steering unit is a dichroic mirror.
Illustratively, the scanning unit is a single scanning galvanometer.
Illustratively, the scanning unit is a spatial light modulator.
Illustratively, the apparatus further comprises a relay unit disposed downstream of the scanning unit, wherein the relay unit is configured to focus the line beam scanned by the scanning unit to the endoscopic unit; the fluorescence is collected by the linear array detection unit after passing through the relay unit, the scanning unit and the steering unit.
Illustratively, the endoscopic unit further comprises a micro objective lens arranged at the other end of the imaging fiber bundle for focusing the line beam conducted by the imaging fiber bundle onto the sample.
Illustratively, the linear array detection unit comprises a focusing lens and a linear array detector which are sequentially arranged, wherein the focusing lens is used for focusing fluorescent light emitted by the sample; and the linear array detector is used for collecting the fluorescent signals after focusing.
The linear array detection unit further comprises a slit for allowing only fluorescence light of the focal plane to pass through, for example.
Illustratively, the linear array detection unit further comprises an optical filter disposed between the focusing lens and the linear array detector for filtering out stray light.
The rapid tissue molecule imaging device adopts a linear light source to excite a sample, adopts a one-dimensional scanning unit to scan a linear light beam, and adopts a linear array detection unit to detect excitation light of the sample so as to realize confocal in one-dimensional direction. The linear beam and the linear array detection unit are combined to image tissue molecules, so that the imaging speed of the tissue molecules can be greatly improved, real-time imaging can be realized, and the scanning unit only performs one-dimensional scanning, so that the stability of the system can be effectively improved.
Drawings
The above and other objects, features and advantages of the present invention will become more apparent from the following more particular description of embodiments of the present invention, as illustrated in the accompanying drawings. The accompanying drawings are included to provide a further understanding of embodiments of the invention and are incorporated in and constitute a part of this specification, illustrate the invention and together with the embodiments of the invention, and not constitute a limitation to the invention. In the drawings, the same reference numbers generally represent the same or similar components or steps.
FIG. 1 shows a schematic block diagram of a rapid tissue molecular imaging apparatus according to one embodiment of the invention;
fig. 2 shows a schematic optical path diagram of a rapid tissue molecular imaging device according to one embodiment of the invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, exemplary embodiments according to the present invention will be described in detail with reference to the accompanying drawings. It should be apparent that the described embodiments are only some embodiments of the present invention and not all embodiments of the present invention, and it should be understood that the present invention is not limited by the example embodiments described herein. Based on the embodiments of the invention described in the present application, all other embodiments that a person skilled in the art would have without inventive effort shall fall within the scope of the invention.
Fig. 1 and 2 schematically illustrate a block diagram and an optical path diagram, respectively, of a rapid tissue molecular imaging apparatus 100 according to one embodiment of the invention. The rapid tissue molecular imaging apparatus 100 includes a light emitting unit 110, a steering unit 120, a scanning unit 130, and a line detection unit 160. The rapid tissue molecule imaging device 100 can be widely applied to tissue molecule imaging of various parts such as digestive tracts, respiratory tracts and the like, and early diagnosis of tumors is realized.
The light emitting unit 110 is for emitting a ray beam. In one embodiment, the light emitting unit 110 may include a light source 112 and a beam expanding line focus 114. The light source 112 is for emitting a collimated light beam. The light source 112 may be a laser that emits collimated laser light of a particular wavelength. The specific wavelength range may be
20nm-2000nm. Laser light in this wavelength range can excite a wide range of phosphors. The light source 112 may be a quantum well laser, a solid state laser, a gas laser (e.g., an argon ion laser), or a laser diode. A beam expanding line focus 114 is disposed at the outlet of the light source 112 for expanding and one-dimensionally focusing the collimated light beam emitted from the light source 112 into a line beam. The expanded beam line focus 114 may include an expanded beam lens and a cylindrical lens. The beam expander lens may include two beam expander lenses L1, L2, and the two beam expander lenses L1, L2 cooperate to expand the collimated light beam emitted from the light source 112 to change the diameter of the collimated light beam. The cylindrical lens includes L3 which one-dimensionally focuses the expanded light beam into a line beam and guides it to the steering unit 120.
The turning unit 120 is located downstream of the light emitting unit 110, for turning the line light beam emitted by the light emitting unit 110, and is capable of transmitting fluorescence of the sample. In fig. 1 and 2, solid lines are used to represent the line beam emitted from the light emitting unit 110, and broken lines are used to represent the fluorescence excited by the sample. The turning unit 120 serves to separate the light emitted from the light emitting unit 110 from fluorescence generated by excitation of the sample. The transmittance of the turning unit 120 for fluorescence may reach more than 90%, while substantially totally reflecting light of other wavelengths. Then, the line beam emitted from the light emitting unit 110 is reflected to the scanning unit 130 while passing through the steering unit 120. The fluorescence returned along the same optical path as the line beam is transmitted while passing through the steering unit 120, and is conducted to the line detection unit 160. The steering unit 120 satisfying the above conditions may be a dichroic mirror. Preferably, the wavelength range of the dichroic mirror may be in the wavelength range of 40nm-2200 nm.
The scanning unit 130 is located downstream of the steering unit 120, and performs one-dimensional sweeping on the steered line beam for adjusting the direction of the steered line beam to scan the sample line by line. Specifically, the line beam may be, for example, a line beam extending in the X direction, and the scanning unit 130 turns the line beam to a downstream optical component (e.g., the relay unit 140) while performing Y-direction scanning. The Y direction is at an angle to the X direction, for example at a right angle of 90 degrees. The scanning unit 130 mainly performs one-dimensional scanning in the Y direction. Thus, the whole image can be formed by performing scanning in the Y direction once in cooperation with the line beam in the X direction. It can be seen that the line beam is combined with the line array detection unit 160 to image line by line, so that the imaging speed is greatly improved compared with the conventional point-by-point imaging. For example, the existing point-by-point imaging system can only obtain one point on the image at a time, assuming that the imaging time of 1 point is 1 μs, for an image of 512×512 pixels, the time required for forming the whole image is 1 μs×512×512=0.26 s, and about 4 images can be formed in 1 second; for the line scanning system provided by the application, one line of image can be obtained once by shooting 1 time, and the theoretical improvement is 512 times compared with the original. Assuming that the camera exposure time is 40 μs, an image can be formed with a time of 40 μs by 512=0.02 s, and about 50 images can be formed in 1 second. Further, since only the sweep in one-dimensional direction is performed, the scanning unit 130 may be a single scanning galvanometer. The frequency of the scanning galvanometer can be in the frequency range of 10-2000 KHz. The single scanning galvanometer can greatly reduce noise, simplify the composition and control complexity of the device, improve the stability of the whole machine, and reduce the manufacturing cost and the maintenance cost. In addition, the scanning unit 130 may be a spatial light modulator. Spatial light modulators are relatively costly compared to scanning galvanometers.
The rapid tissue molecular imaging apparatus 100 further includes a relay unit 140 and an endoscopic unit 150 disposed downstream of the scanning unit 130.
The relay unit 140 is used to focus the line beam scanned by the scanning unit 130 to the endoscopic unit 150. The relay unit 140 is typically a lens group, such as lenses L4, L5.
The endoscopic unit 150 serves to guide and focus the line beam focused by the relay unit 140 onto the sample and to receive fluorescence emitted from the sample. The fluorescence is collected by the linear array detection unit 160 after passing through the relay unit 140 and the steering unit 120. The endoscopic unit 150 may include a coupling objective 152, a micro objective 156, and an imaging fiber bundle 154 coupled between the coupling objective 152 and the micro objective 156. The relay unit 140 may include two relay lenses L4, L5 that cooperate to relay the scanned line beam to the rear pupil of the coupling objective 152 in the endoscopic unit 150. The coupling objective 152 is used to couple (e.g., focus) the line beam into the proximal end (end near the operator) of the imaging fiber bundle 154. The imaging fiber bundle 154 is used to conduct the line beam to the distal end (the end remote from the operator) of the imaging fiber bundle 154. The micro objective 156 is used to focus the laser light conducted by the imaging fiber bundle 154 onto the detection surface of the sample. The detection surface may be located at a desired depth below the surface of the sample. The fluorophore at the detection face of the sample is stimulated to fluoresce. The fluorescent signal is collected by the micro objective 156, conducted by the imaging fiber bundle 154, the coupling objective 152 and the relay unit 140, reflected by the scanning unit 130, and passed through the steering unit 120 to the linear array detection unit 160. The imaging fiber bundle 154 may include more than ten bundles of light rays. The micro objective 156 is not necessary. In cases where the sharpness requirements are not high, the micro objective 156 may optionally be omitted. The micro-objective 156 may be designed to extend into and contact the surface of the alimentary tract, respiratory tract, etc.
On the detection light path, the linear array detection unit 160 collects fluorescence returned through the endoscope unit 150, the relay unit 140, the scanning unit 130, and the steering unit 120 in this order. In a preferred embodiment, the linear array detection unit 160 includes a focusing lens 162 and a linear array detector 166. The focusing lens 162 is used to focus the fluorescence emitted from the sample. The linear array detector 166 is used for collecting the fluorescent signal focused by the focusing lens 162. The focused fluorescence is sensed on the photosensitive surface of the linear array detector 166. The line detector 166 may be various types of line cameras, such as a CCD (charge coupled device) line camera or a CMOS (complementary metal oxide semiconductor) line camera, or the like. The imaging speed of the line detector 166 is in the range of tens of frames to tens of millions of frames.
Optionally, a slit 164 may be provided between the focusing lens 162 and the line detector 166, the slit 164 being adapted to allow only fluorescence light of the focal plane to pass. The size of the slit 164 may be in the range of several tens of nanometers to several tens of millimeters. The presence of the slit 164 allows stray light out of the focal plane to be blocked. Only the fluorescence emitted from the sample illuminated by the line beam on the focal plane is received, and by the scanning of the scanning unit 130, the fluorescence emitted from the sample in all the rows of the sample at the focal plane is received by the line detector 166 and arranged in a two-dimensional image according to the scanned trajectory, so that an observable tissue molecular image can be rapidly realized. Alternatively, the line detection unit 160 includes an optical filter. A filter (not shown) is provided between the focusing lens 162 and the line detector 166 for filtering out stray light. In embodiments with a slit 164, a filter may be disposed between the focusing lens 162 and the slit 164.
In summary, the collimated light beam emitted by the light source 112 is expanded by the beam expander and focused into a linear light beam in one dimension by the beam expander and focused device 114, the linear light beam is deflected by the deflecting unit 120, the linear light beam is coupled into the endoscope unit 150 by the scanning unit 130 through the relay unit 140, the laser beam is conducted to the sample by the endoscope unit 150, and fluorescence is excited and transferred back to the array detection unit 160 for imaging.
For example, the data collected by the linear array detector may be sent to a computer, received by the computer, and processed. In addition, the computer can also control the scanning unit (such as the frequency of a vibrating mirror, etc.), the exposure and gain of the linear array detector, the transmitting power of the light transmitting unit, etc.
The rapid tissue molecular imaging apparatus 100 excites a sample using a line light source, scans a line beam using a one-dimensional scanning unit 130 (e.g., a single scanning galvanometer), and detects the excitation light of the sample using a line array detection unit 160, achieving confocal in one-dimensional directions. The linear beam and the linear array detection unit 160 are combined to image tissue molecules, so that the imaging speed of tissue molecules can be greatly improved, real-time imaging can be realized, and the scanning unit 130 only performs one-dimensional scanning, so that the stability of the system can be effectively improved.
Although the illustrative embodiments have been described herein with reference to the accompanying drawings, it is to be understood that the above illustrative embodiments are merely illustrative and are not intended to limit the scope of the present invention thereto. Various changes and modifications may be made therein by one of ordinary skill in the art 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 set forth in the appended claims.
In the several embodiments provided in this application, it should be understood that the disclosed apparatus and method may be implemented in other ways. For example, the above-described device embodiments are merely illustrative, e.g., the division of the elements is merely a logical functional division, and there may be additional divisions when actually implemented, e.g., multiple elements or components may be combined or integrated into another device, or some features may be omitted or not performed.
In the description provided herein, numerous specific details are set forth. However, it is understood that embodiments of the invention may be practiced without these specific details. In some instances, well-known methods, structures and techniques have not been shown in detail in order not to obscure an understanding of this description.
Similarly, it should be appreciated that in order to streamline the invention and aid in understanding one or more of the various inventive aspects, various features of the invention are sometimes grouped together in a single embodiment, figure, or description thereof in the description of exemplary embodiments of the invention. However, the method of the present invention should not be construed as reflecting the following intent: i.e., the claimed invention requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects lie in less than all features of a single disclosed embodiment. Thus, the claims following the detailed description are hereby expressly incorporated into this detailed description, with each claim standing on its own as a separate embodiment of this invention.
It will be understood by those skilled in the art that all of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and all of the processes or units of any method or apparatus so disclosed, may be combined in any combination, except combinations where the features are mutually exclusive. Each feature disclosed in this specification (including any accompanying claims, abstract and drawings), may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise.
Furthermore, those skilled in the art will appreciate that while some embodiments described herein include some features but not others included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention and form different embodiments. For example, in the claims, any of the claimed embodiments may be used in any combination.
It should be noted that the above-mentioned embodiments illustrate rather than limit the invention, and that those skilled in the art will be able to design alternative embodiments without departing from the scope of the appended claims. In the claims, any reference signs placed between parentheses shall not be construed as limiting the claim. The word "comprising" does not exclude the presence of elements or steps not listed in a claim. The word "a" or "an" preceding an element does not exclude the presence of a plurality of such elements. The invention may 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 may be embodied by one and the same item of hardware. The use of the words first, second, third, etc. do not denote any order. These words may be interpreted as names.
The foregoing description is merely illustrative of specific embodiments of the present invention and the scope of the present invention is not limited thereto, and any person skilled in the art can easily think about variations or substitutions within the scope of the present invention. The protection scope of the invention is subject to the protection scope of the claims.
Claims (9)
1. The utility model provides a quick tissue molecule image device, includes light emission unit, turns to unit, scanning unit, peep unit and linear array detection unit, wherein:
the light emitting unit comprises a light source and a beam expanding line focus device, wherein the light source is used for emitting a collimated light beam, the beam expanding line focus device is arranged at an outlet of the light source and comprises a beam expanding lens and a cylindrical lens, the beam expanding lens is used for expanding the collimated light beam emitted by the light source so as to change the diameter of the collimated light beam, and the cylindrical lens is used for one-dimensionally focusing the expanded light beam into a line light beam;
the steering unit is used for steering the linear light beam and transmitting fluorescence of the sample;
the scanning unit is used for adjusting the direction of the turned linear light beam to scan the sample line by line;
the endoscope unit is used for conducting and focusing the focused line light beam onto a sample and receiving fluorescence emitted by the sample, and comprises a coupling objective lens and an imaging optical fiber beam, wherein the coupling objective lens is arranged at one end of the imaging optical fiber beam and is used for coupling the focused line light beam into the proximal end of the imaging optical fiber beam, and the imaging optical fiber beam is used for conducting the incoming line light beam; and
the linear array detection unit is used for collecting the fluorescence.
2. The apparatus of claim 1, wherein the steering unit is a dichroic mirror.
3. The apparatus of claim 1, wherein the scanning unit is a single scanning galvanometer.
4. The apparatus of claim 1, wherein the scanning unit is a spatial light modulator.
5. The apparatus of claim 1, wherein the apparatus further comprises a relay unit disposed downstream of the scanning unit, wherein
The relay unit is used for focusing the line light beam scanned by the scanning unit to the endoscopic unit;
the fluorescence is collected by the linear array detection unit after passing through the relay unit, the scanning unit and the steering unit.
6. The apparatus of claim 1, wherein the endoscope unit further comprises a micro objective lens disposed at the other end of the imaging fiber bundle for focusing the line beam conducted by the imaging fiber bundle onto the sample.
7. The apparatus of claim 1, wherein the linear array detection unit comprises a focusing lens and a linear array detector disposed in sequence, wherein
The focusing lens is used for focusing fluorescence emitted by the sample; and
the linear array detector is used for collecting the fluorescent signals after focusing.
8. The apparatus of claim 7, wherein the linear array detection unit further comprises a slit for allowing only fluorescence of the focal plane to pass.
9. The apparatus of claim 7, wherein the linear array detection unit further comprises a filter disposed between the focusing lens and the linear array detector for filtering out stray light.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710598023.0A CN107361725B (en) | 2017-07-20 | 2017-07-20 | Quick tissue molecule imaging device |
| PCT/CN2018/091979 WO2019015438A1 (en) | 2017-07-20 | 2018-06-20 | Device for fast imaging of tissue molecule |
| TW107124996A TWI674883B (en) | 2017-07-20 | 2018-07-19 | Rapid tissue molecule imaging device |
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| CN201710598023.0A CN107361725B (en) | 2017-07-20 | 2017-07-20 | Quick tissue molecule imaging device |
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| CN107361725A CN107361725A (en) | 2017-11-21 |
| CN107361725B true CN107361725B (en) | 2024-02-27 |
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| CN107361725B (en) * | 2017-07-20 | 2024-02-27 | 无锡海斯凯尔医学技术有限公司 | Quick tissue molecule imaging device |
| CN107361723B (en) * | 2017-07-20 | 2024-02-13 | 无锡海斯凯尔医学技术有限公司 | Quick tissue molecular spectrum imaging device |
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| WO2019015438A1 (en) | 2019-01-24 |
| TWI674883B (en) | 2019-10-21 |
| CN107361725A (en) | 2017-11-21 |
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