WO2019015438A1

WO2019015438A1 - Device for fast imaging of tissue molecule

Info

Publication number: WO2019015438A1
Application number: PCT/CN2018/091979
Authority: WO
Inventors: 王强; 邵金华; 孙锦; 段后利
Original assignee: 无锡海斯凯尔医学技术有限公司
Priority date: 2017-07-20
Filing date: 2018-06-20
Publication date: 2019-01-24
Also published as: TW201907872A; CN107361725B; TWI674883B; CN107361725A

Abstract

A device for fast imaging of a tissue molecule (100) comprises a light transmitting unit (110), a diversion unit (120), a scanning unit (130), and a linear array detecting unit (160). The light transmitting unit (110) is used to transmit a linear light beam. The diversion unit (120) is used to divert the linear light beam and allows fluorescent light emitted by a sample to pass therethrough. The scanning unit (130) is used to adjust a direction of the diverted linear light beam to scan the sample line by line. The linear array detecting unit (160) is used to collect the fluorescent light. The device for fast imaging of a tissue molecule (100) adopts a linear light source (112) to excite a sample, uses a one-dimensional scanning unit to perform scanning with a linear light beam, and uses a linear array detecting unit (160) to detect the excited light of the sample, thereby realizing cofocusing in a one-dimensional direction. The linear light beam and the linear array detecting unit (160) are used in combination to perform imaging of a tissue molecule, thereby significantly increasing a speed of imaging the tissue molecule, and realizing real-time imaging. Moreover, the scanning unit (130) only performs one-dimensional scanning, thereby effectively increasing system stability.

Description

Rapid tissue molecular imaging device

Technical field

The present invention relates to the field of medical devices, and more particularly to a rapid tissue molecular imaging device.

Background technique

Tumors are major diseases that pose a serious threat to human health. 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 rapid organization molecular imaging apparatus comprising a light emitting unit, a steering unit, a scanning unit and a line array detecting unit, wherein the light emitting unit is for emitting a line beam; the steering unit is for steering the line The light beam is transmitted through the fluorescence of the sample; the scanning unit is configured to adjust the direction of the steered line beam to scan the sample line by line; and the line 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 expander focus concentrator disposed at an exit of the light source for expanding and collimating the collimated beam For the line beam.

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 includes a relay unit and an endoscope unit disposed downstream of the scanning unit, wherein the relay unit is configured to focus a line beam scanned by the scanning unit to the endoscopic unit The endoscope unit is configured to conduct and focus the focused line beam onto the sample and receive fluorescence emitted by the sample; the fluorescence is passed by the relay unit, the scanning unit, and the steering unit Line array detection unit acquisition.

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 line beam into a proximal end of the fiber bundle And the imaging fiber bundle is used to conduct incoming line beams.

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 line array detecting unit includes a focusing lens and a line array detector which are sequentially disposed, wherein the focusing lens is used to focus the fluorescence emitted by the sample; and the line array detector is used to collect the focused Fluorescent signal.

Illustratively, the line array detecting unit further includes a slit for allowing only the fluorescence of the focus plane to pass.

Illustratively, the line array detecting unit further includes a filter disposed between the focus lens and the line array detector for filtering out stray light.

The fast tissue molecular imaging device uses a line source to excite the sample, scans the line beam with a one-dimensional scanning unit, and uses the line array detection unit to detect the sample excitation light, achieving confocal in one dimension. Due to the combination of the line beam and the line array detecting unit for tissue molecular imaging, the imaging speed of the tissue molecules can be greatly improved, real-time imaging can be realized, and since the scanning unit performs only one-dimensional scanning, the stability of the system can be effectively improved.

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 rapid tissue molecular imaging apparatus in accordance with one embodiment of the present invention;

2 shows a schematic diagram of an optical path of a fast tissue molecular 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 block diagrams and optical path diagrams, respectively, of a rapid tissue molecular imaging apparatus 100 in accordance with one embodiment of the present invention. The fast tissue molecular imaging apparatus 100 includes a light emitting unit 110, a steering unit 120, a scanning unit 130, and a line array detecting unit 160. The rapid tissue molecular 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 line beam. In one embodiment, light emitting unit 110 can include a light source 112 and a beam expander focus concentrator 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 focus concentrator 114 is disposed at the exit of the light source 112 for expanding the collimated beam of light from the source 112 and focusing it in one dimension into a line beam. The beam expander focus concentrator 114 can include a beam expander lens and a cylindrical lens. The beam expander lens may include two L1, L2, and the two beam expanders L1, L2 cooperate to expand the collimated beam emitted by the light source 112 to change the diameter of the collimated beam. The cylindrical lens includes L3 that focuses the expanded beam into a line beam and conducts it to the steering unit 120.

The steering unit 120 is located downstream of the light emitting unit 110 for turning to the line beam emitted by the light emitting unit 110 and capable of transmitting the fluorescence of the sample. In Figs. 1 and 2, a solid line is used to indicate a line beam emitted from the light-emitting unit 110, and a broken line is used to indicate that the sample is excited by fluorescence. The steering unit 120 is for separating the light emitted by the light emitting unit 110 and the fluorescence generated by the excitation of the sample. 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 line beam emitted from the light emitting unit 110 is reflected to the scanning unit 130 through the steering unit 120. Fluorescence returned along the same optical path as the line beam is transmitted through the steering unit 120 and conducted to the line array detecting unit 160. 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 scanning unit 130 is located downstream of the steering unit 120 and performs a one-dimensional sweep of 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 diverts the line beam to a downstream optical component (for example, 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 entire image can be formed by performing a scanning in the Y direction in cooperation with the line beam in the X direction. It can be seen that the line beam combining line array detecting unit 160 can image line by line, so the imaging speed is greatly improved compared to the existing point-by-point imaging. For example, an existing point-by-point imaging system can only get one point on the image at a time, assuming that 1 point is imaged for 1 μs, and for a 512*512 pixel image, the time required for the entire image 1μs*512*512=0.26s, about 4 images in 1 second; and for the line scanning system provided by the present application, one line of image can be obtained once in a single shot, which is theoretically 512 times higher than the original. Assuming that the camera has an exposure time of 40 μs, the image time is 40 μs* 512 = 0.02 s, and approximately 50 images can be made in one second. Further, since only the sweep in the 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 use of a single scanning galvanometer can greatly reduce noise, and the complexity of the composition and control of the device improves the stability of the whole machine while reducing manufacturing costs and maintenance costs. Further, the scanning unit 130 can also be a spatial light modulator. Spatial light modulators are relatively expensive compared to scanning galvanometers.

The fast tissue molecular imaging apparatus 100 further includes a relay unit 140 and an endoscope unit 150 disposed downstream of the scanning unit 130.

The relay unit 140 is configured to focus the line beam scanned by the scanning unit 130 to the endoscope unit 150. The relay unit 140 is typically a lens group, such as lenses L4, L5.

The endoscope unit 150 is configured to conduct and focus the line beam focused by the relay unit 140 onto the sample and receive the fluorescence emitted by the sample. The fluorescence is collected by the line array detecting unit 160 via the relay unit 140 and the steering unit 120. The endoscopic unit 150 can include a coupling objective 152, a miniature 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 endoscope unit 150. The coupling objective 152 is used to couple (e.g., focus) the line beam into the proximal end of the imaging fiber bundle 154 (near the operator's end). The imaging fiber bundle 154 is used to conduct a line beam to the distal end of the imaging fiber bundle 154 (away from the end of the operator). The miniature objective lens 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 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 156, transmitted through the imaging fiber bundle 154, the coupling objective lens 152, and the relay unit 140, and the scanning unit 130 reflects and passes through the steering unit 120 to enter the line array detecting unit 160. The number of bundles of light included in the imaging fiber bundle 154 can be greater than ten. The miniature objective lens 156 is not required. In the case where the definition is not high, the micro objective lens 156 may alternatively be omitted. The micro objective lens 156 can be designed to extend into the digestive tract, the respiratory tract, and the like, and is in contact with the surface of the digestive tract, the respiratory tract, and the like.

On the probe optical path, the line array detecting unit 160 collects fluorescence that is sequentially returned through the endoscope unit 150, the relay unit 140, the scanning unit 130, and the steering unit 120. In a preferred embodiment, line array detection unit 160 includes a focus lens 162 and a line array detector 166. A focusing lens 162 is used to focus the fluorescence emitted by the sample. The line array detector 166 is used to collect the fluorescent signal after the focus lens 162 is focused. The focused fluorescent array detector 166 is photosensitive on the photosensitive surface. The line array detector 166 may be various types of line array cameras such as a CCD (Charge Coupled Device) line array camera or a CMOS (Complementary Metal Oxide Semiconductor) line array camera. The imaging speed of the line array detector 166 is in the range of several tens of frames to tens of millions of frames.

Alternatively, a slit 164 may be provided between the focusing lens 162 and the line array detector 166 for allowing only the fluorescence of the focal plane to pass. The size of the slit 164 may range from several tens of nanometers to several tens of millimeters. The presence of the slit 164 causes stray light outside the focus plane to be blocked. Only the fluorescence emitted by the line beam illuminating the sample on the focus plane is received, and the fluorescence emitted by the sample of all the rows of the sample at the focus plane is received by the line detector 166 by the scanning of the scanning unit 130, and arranged according to the scanning trajectory. It is a two-dimensional image, which can quickly realize observable tissue molecular images. Optionally, the line array detection unit 160 includes a filter. A filter (not shown) is disposed between the focus lens 162 and the line detector 166 for filtering out stray light. In embodiments having slits 164, a filter can be disposed between focusing lens 162 and slit 164.

In summary, the collimated beam emitted by the light source 112 is expanded by the beam expander concentrator 114 and concentrated into a line beam in one dimension, the steering unit 120 folds the line beam, and the scanning unit 130 couples the line beam through the relay unit 140. Entering the endoscopic unit 150, the endoscopic unit 150 conducts the laser beam to the sample, excites the fluorescence, and passes it back to the line array detecting unit 160 for imaging.

Illustratively, data collected by a line array detector can be sent to a computer for receipt and processing by a computer. In addition, the computer can also control the scanning unit (such as the frequency of the galvanometer, etc.), the exposure and gain of the line array detector, and the transmission power of the light emitting unit.

The fast tissue molecular imaging device 100 uses a line source to excite the sample, scans the line beam with a one-dimensional scanning unit 130 (eg, a single scanning galvanometer), and uses the line array detecting unit 160 to detect the sample excitation light in one dimension. The direction is achieved by confocal. Since the line beam is combined with the line array detecting unit 160 for tissue molecular imaging, the imaging speed of the tissue molecules can be greatly improved, real-time imaging can be realized, and since the scanning unit 130 performs only one-dimensional scanning, the stability of the system can be effectively improved. .

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 rapid organization molecular imaging device comprising a light emitting unit, a steering unit, a scanning unit and a line array detecting unit, wherein:

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

The steering unit is configured to turn the line beam and transmit fluorescence of the sample;

The scanning unit is configured to adjust a direction of the steered line beam to scan the sample line by line;

The line 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 focus concentrator is disposed at the exit of the light source for expanding the collimated beam and focusing it in one dimension into a line beam.
The apparatus of claim 1 wherein said steering unit is a dichroic mirror.
The apparatus of claim 1 wherein said scanning unit is a single scanning galvanometer.
The apparatus of claim 1 wherein said scanning unit is a spatial light modulator.
The apparatus of claim 1, wherein the apparatus further comprises a relay unit and an endoscope unit disposed downstream of the scanning unit, wherein

The relay unit is configured to focus a line beam scanned by the scanning unit to the endoscope unit;

The endoscope unit is configured to conduct and focus the focused line beam onto the sample and receive fluorescence emitted by the sample;

The fluorescence is collected by the line array detecting unit after the relay unit, the scanning unit, and 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 line beam into a proximal end of the bundle;

The imaging fiber bundle is used to conduct incoming line beams.
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 rays for focusing a beam of light guided by said bundle of fibers to On the sample.
The apparatus according to claim 1, wherein said line array detecting unit comprises a focus lens and a line array detector which are sequentially disposed, wherein

The focusing lens is for focusing a fluorescent light emitted by the sample;

The line array detector is used to collect the focused fluorescent signal.
The apparatus according to claim 9, wherein said line array detecting unit further comprises a slit for allowing only fluorescence of a focus plane to pass.
The apparatus according to claim 9, wherein said line array detecting unit further comprises a filter disposed between said focus lens and said line array detector for filtering out stray light .