CN108937824A - A kind of acquisition methods of based endoscopic imaging device and Fluorescence lifetime distribution image - Google Patents
A kind of acquisition methods of based endoscopic imaging device and Fluorescence lifetime distribution image Download PDFInfo
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Classifications
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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
- A61B1/00002—Operational features of endoscopes
- A61B1/00004—Operational features of endoscopes characterised by electronic signal processing
- A61B1/00009—Operational features of endoscopes characterised by electronic signal processing of image signals during a use of endoscope
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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
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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
- A61B1/00163—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
- A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
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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
- A61B5/0075—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
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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 invention discloses the acquisition methods of a kind of based endoscopic imaging device and Fluorescence lifetime distribution image, based endoscopic imaging device includes laser transmission module, interior peeps module and fluorescence lifetime imaging module；Laser transmission module includes laser, dichroscope, scanning galvanometer and lens set, inside peeping module includes image-carrying fiber bundle and miniature graded index prism, and the transmission that the laser that laser issues successively passes through dichroscope, scanning galvanometer, lens set, image-carrying fiber bundle is projected from miniature graded index prism；Fluorescence lifetime imaging module includes optical filter, single photon counter and controller, optical filter is between dichroscope and single photon counter, controller is connect with single photon counter, laser and scanning galvanometer, the light injected from miniature graded index prism successively passes through image-carrying fiber bundle, lens set, scanning galvanometer, dichroscope and optical filter and reaches single photon counter, fluorescence lifetime can be detected and be applied in clinical detection through the invention, facilitate the diagnosis of disease.
Description
Technical field
The present invention relates to micro-imaging technique neck field more particularly to a kind of based endoscopic imaging devices and Fluorescence lifetime distribution figure
The acquisition methods of picture.
Background technique
Currently, traditional bio-imaging means such as fluorescence intensity imaging technique is mainly characterized by signal strength, however believe
Number intensity is often by imaging depth, and the conditions such as marker concentrations influence, and measurement accuracy and quantitative analysis ability are all undesirable.Phase
Than under, fluorescence lifetime imaging technology issues the life information of fluorescence as signal after being stimulated using marker, it is dense by marker
The influence of degree and excitation light intensity is minimum, and is influenced by cell micro-environment (such as pH value, oxygen saturation, viscosity and ion concentration)
It is larger.Therefore, fluorescence lifetime imaging technology is often used to accurately monitor cell micro-environment, in cell the release of drug with move
It moves, these have much use in cancer auxiliary monitoring.
However common fluorescence lifetime imaging system is only for cell sample or histotomy, it is difficult to be applied to clinical original
In the detection of position.If can be by fluorescence lifetime imaging technical application into clinical detection, it will effect and transmission mechanism to drug,
The tentative diagnosis of cancer generates active influence.
Summary of the invention
The main purpose of the embodiment of the present invention is to provide obtaining for a kind of based endoscopic imaging device and Fluorescence lifetime distribution image
Method is taken, the accuracy to medical diagnosis on disease can be promoted by fluorescence lifetime imaging technical application into clinical in situ detection.
To achieve the above object, first aspect of the embodiment of the present invention provides a kind of based endoscopic imaging device, based endoscopic imaging dress
To set include: laser transmission module, interior peeps module and fluorescence lifetime imaging module；
The laser transmission module includes laser, dichroscope, scanning galvanometer and lens set, it is described in peep module and include
Image-carrying fiber bundle and the miniature graded index prism connecting with the image-carrying fiber bundle, the laser that the laser issues is successively
One end that the image-carrying fiber bundle is reached by the dichroscope, scanning galvanometer and lens set, through the image-carrying fiber bundle
Transmission is projected from the miniature graded index prism；
The fluorescence lifetime imaging module includes optical filter, the single photon meter with number of photons statistics and photoelectric conversion function
Number device and the controller with spectrum analysis function, the optical filter are located at the dichroscope and the single photon counter
Between, the controller is connect with the single photon counter, the laser and the scanning galvanometer, from it is described it is miniature gradually
The light that variable refractivity prism is injected successively passes through the image-carrying fiber bundle, lens set, scanning galvanometer, dichroscope and the optical filtering
Piece reaches the single photon counter.
To achieve the above object, second aspect of the embodiment of the present invention provides a kind of acquisition side of Fluorescence lifetime distribution image
Method, the acquisition methods of the Fluorescence lifetime distribution image are based on above-mentioned based endoscopic imaging device realization, the Fluorescence lifetime distribution image
Acquisition methods include:
The laser emits laser；
The laser through the dichroscope is successively scanned the difference to the image-carrying fiber bundle by the scanning galvanometer
On optical fiber, wherein the laser reaches the optical fiber of the image-carrying fiber bundle after scanning galvanometer injection through the lens set
Different optical fiber；
The laser is imported the miniature graded index prism by the image-carrying fiber bundle, to irradiate the miniature gradual change
Target area under index prism, wherein injection has fluorescent dye in the target area；
From the fluorescence of the miniature graded index prism incidence by the image-carrying fiber bundle, lens set, scanning galvanometer,
Dichroscope and the optical filter are transferred to the single photon counter, and the fluorescence is by the fluorescent dye through the laser
Excitation generates；
The single photon counter carries out photoelectric conversion according to the fluorescence, and the result of conversion is sent to the control
Device；
The controller determines the fluorescent dye in the Fluorescence lifetime distribution image of target area according to the result.
The embodiment of the invention provides the acquisition methods of a kind of based endoscopic imaging device and Fluorescence lifetime distribution image, the present invention
Based endoscopic imaging device include laser transmission module, interior peep module and fluorescence lifetime imaging module；Laser transmission module includes swashing
Light device, dichroscope, scanning galvanometer and lens set, inside peeping module includes image-carrying fiber bundle and miniature graded index prism, is swashed
The laser that light device issues successively passes through one end that dichroscope, scanning galvanometer and lens set reach image-carrying fiber bundle, through passing as light
The transmission of fine beam is projected from miniature graded index prism；Fluorescence lifetime imaging module includes optical filter, has number of photons statistics
With the single photon counter of photoelectric conversion function and the controller with spectrum analysis function, optical filter be located at dichroscope and
Between single photon counter, controller is connect with single photon counter, laser and scanning galvanometer, from miniature graded index
The light that prism is injected successively passes through image-carrying fiber bundle, lens set, scanning galvanometer, dichroscope and optical filter and reaches single photon counting
Device, based endoscopic imaging device through the invention can inject fluorescence in the area to be tested (or affected areas) to inside of human body
After dyestuff, fluorescence lifetime image is obtained to the area to be tested of inside of human body, to determine cell micro-environment in the area to be tested
Situation, the distribution situation etc. of fluorescent dye promotes the accuracy of medical diagnosis on disease.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
Some embodiments of invention for those skilled in the art without creative efforts, can also basis
These attached drawings obtain other attached drawings.
Fig. 1 is a kind of structural schematic diagram of based endoscopic imaging device in the embodiment of the present invention；
Fig. 2 is the structural schematic diagram of another based endoscopic imaging device in the embodiment of the present invention；
Fig. 3 is the structural schematic diagram of another based endoscopic imaging device in the embodiment of the present invention；
Fig. 4 is a kind of flow chart of the acquisition methods of Fluorescence lifetime distribution image in the embodiment of the present invention；
Fig. 5 is the flow chart of the acquisition methods of another Fluorescence lifetime distribution image in the embodiment of the present invention.
Specific embodiment
In order to make the invention's purpose, features and advantages of the invention more obvious and easy to understand, below in conjunction with the present invention
Attached drawing in embodiment, technical scheme in the embodiment of the invention is clearly and completely described, it is clear that described reality
Applying example is only a part of the embodiment of the present invention, and not all embodiments.Based on the embodiments of the present invention, those skilled in the art
Member's every other embodiment obtained without making creative work, shall fall within the protection scope of the present invention.
Lack in the prior art it is a kind of by fluorescence lifetime imaging technical application to the scheme in clinical in situ detection, to understand
Certainly this problem, the present embodiment propose a kind of based endoscopic imaging device, the hardware based on the based endoscopic imaging device that the present embodiment proposes
Structure can detect the position to be detected of inside of human body by fluorescence lifetime imaging technology, to obtain part to be detected
The case where, helping to treat detection position, whether illness and the specific state of an illness have deep understanding, especially to the preliminary of cancer
Diagnosis generates positive influence.
Referring to Fig. 1, the present embodiment proposes a kind of based endoscopic imaging device, the based endoscopic imaging device include: laser transmission module,
Inside peep module and fluorescence lifetime imaging module；
Laser transmission module includes laser 11, dichroscope 12, scanning galvanometer 13 and lens set 14, and inside peeping module includes
Image-carrying fiber bundle 15 and the miniature graded index prism 16 connecting with image-carrying fiber bundle 15, the laser that laser 11 issues is successively
One end of image-carrying fiber bundle 15, the biography through image-carrying fiber bundle 15 are reached by dichroscope 12, scanning galvanometer 13 and lens set 14
It is defeated to be projected from miniature graded index prism 16.When interior module of peeping has been positioned inside of human body, miniature graded index prism pair
Quasi- (or abutting) position to be detected, then the laser of laser transmitting can reach portion to be detected by miniature graded index prism
, in order to realize the fluorescence lifetime detection for treating detection position in the present embodiment, injected on position to be detected has in advance
The load medicine fluorescent dye of targeting, under the excitation of the laser of laser transmitting, fluorescent dye issues fluorescence.Mirror in the present embodiment
Piece group also has the function of being focused laser, the laser for being transferred to image-carrying fiber bundle is that lens set is poly- in addition to transmitting laser
Laser after coke.
Fluorescence lifetime imaging module includes optical filter 17, the single photon counting with number of photons statistics and photoelectric conversion function
Device 18 and controller 19 with spectrum analysis function, optical filter 17 be located at dichroscope 12 and single photon counter 18 it
Between, controller 19 is connect with single photon counter 18, laser 11 and scanning galvanometer 13, from miniature graded index prism 16
The light of injection successively passes through image-carrying fiber bundle 15, lens set 14, scanning galvanometer 13, dichroscope 12 and optical filter 17 and reaches monochromatic light
Sub-count device 18.
The effect of the optical filter of the present embodiment includes filtering out the laser that laser issues to pass after dichroscope to optical filter
Defeated part reduces interference of the laser to fluorescence lifetime imaging, so the laser that the parameter of optical filter can need to filter out according to it
Wave-length coverage select, the present embodiment do not limit this.In order to go deep into inside of human body detection, the image transmission optical fibre of the present embodiment
Beam has flexible structure.
In Fig. 1 and Fig. 2 and Fig. 3, the lines of grey indicate the path of optical transport, it is contemplated that lens set 14
The transmission path of light, such as the shell of setting tubulose, lens set peace can be guaranteed by certain structure between image-carrying fiber bundle
In the tube-like envelope, one end of image-carrying fiber bundle is directed at connection with a nozzle of tube-like envelope, tube-like envelope it is another
A nozzle is aligned with light-emitting window of the laser on scanning galvanometer.
In the present embodiment, there are multiple fiber cores in image-carrying fiber bundle, scanning galvanometer can will be transmitted from dichroscope
Laser successively scans on the different fiber cores of image-carrying fiber bundle.The laser irradiation of every fiber core transmission is to portion to be detected
Position can all excite fluorescent dye on position to be detected to shine, the fluorescence that the region of every fiber core irradiation issues further through
Miniature graded index prism enters corresponding fiber core, then passes through lens set 14, scanning galvanometer 13, dichroscope 12 and filter
Mating plate 17 reaches single photon counter 18.Single photon counter is counted to photon and is carried out photoelectric conversion, and photoelectricity is turned
The result of change is sent to controller 19, and controller 19 obtains the fluorescent image of area to be tested, wherein because in image-carrying fiber bundle
Optical fiber interval, grid is had on the fluorescent image, controller can carry out denoising by Gaussian filter algorithm, remove glimmering
Grid in light image, the fluorescent image corrected using other processing.Based on fluorescent image or single photon counting
The other information that device obtains finally obtains the Fluorescence lifetime distribution image of area to be tested.
Referring to fig. 2, in an example of the present embodiment, based endoscopic imaging device further includes shell 10, above-mentioned laser 11,
Dichroscope 12, scanning galvanometer 13, lens set 14, optical filter 17 and single photon counter 18 are arranged in shell 10, control
Display panel module is additionally provided on device, display screen and the mechanical button of controller of the display panel module etc. expose to above-mentioned outer
Shell, other controller parts are located in shell, and display panel module can be used for showing the data such as Fluorescence lifetime distribution image.This reality
Switch button can also be arranged in the laser for applying example, which exposes to shell.Optionally, display panel module can also have
There is touch function, easier mode of operation is provided for user, in the controller and laser, scanning galvanometer and list of the present embodiment
It, can be by the touch function of display panel module, to laser, scanning galvanometer, single photon meter on the basis of photon counter connection
The opening and closing of number device and working condition are controlled.
Optionally, as shown in Fig. 2, the lens set 14 of based endoscopic imaging device includes flat field in an example of the present embodiment
Lens 141, cylinder mirror 142 and focusing objective len 143.Cylinder mirror 142 is between field flattening lens 141 and focusing objective len 143, field flattening lens
141 are positioned close to 13 side of scanning galvanometer, and focusing objective len 143 is positioned close to 15 side of image-carrying fiber bundle, are shaken by scanning
The laser of mirror successively passes through field flattening lens, cylinder mirror and focusing objective len and reaches image-carrying fiber bundle.It is, of course, understood that this reality
The lens set for applying example is not limited to be made of field flattening lens, cylinder mirror and focusing objective len according to the structure in Fig. 2, can also be by other
The lens combination that identical function can be achieved forms.The parameter of the eyeglasses such as field flattening lens 141, cylinder mirror 142 and focusing objective len 143, example
Such as thickness, refractive index, focal length of focusing lens etc. can select according to the actual needs, and the present embodiment is not limited in this respect.
In the present embodiment, the optical path between laser 11 and dichroscope 12 is the first optical path, dichroscope 12 and scanning
Optical path between galvanometer 13 is the second optical path, and the optical path between dichroscope 12 and optical filter 17 is third optical path.Referring to Fig. 1,
First optical path and the second optical path are on a horizontal linear, and third optical path is perpendicular to the first optical path and the second optical path, laser
The laser of sending is by the transmission of dichroscope to scanning galvanometer；The light injected from miniature graded index prism successively passes through
The transmission for crossing image-carrying fiber bundle, lens set and scanning galvanometer reaches dichroscope, passes through optical filter after the reflection of dichroscope
Transmission reach single photon counter.
However, it will be understood that in the present embodiment, laser, dichroscope, scanning galvanometer, single photon counter
Deng the setting of relative position be not mode in only Fig. 1.Referring to Fig. 3, in another example of the present embodiment, third
On a horizontal linear, the first optical path is sent out perpendicular to the second optical path and third optical path, laser 11 for optical path and the second optical path
Laser out is by the transmission and reflection of dichroscope 12 to scanning galvanometer 13；From miniature graded index prism 16 inject light according to
The secondary transmission by image-carrying fiber bundle 15, lens set 14 (including 141-143) and scanning galvanometer 13 reaches dichroscope 12, through two
To after the transmission of Look mirror 12, single photon counter 18 is reached by optical filter 17.
In Fig. 1, scanning galvanometer, field flattening lens, cylinder mirror and focusing objective len are located at perpendicular in the optical path of the second optical path, this
In another example of embodiment, scanning galvanometer, field flattening lens, cylinder mirror and focusing objective len can also be adjusted, so that sweeping
Galvanometer, field flattening lens, cylinder mirror and focusing objective len and the second optical path are retouched on the same line, it is, of course, understood that passing as light
The position of fine beam is also required to be varied to therewith to enter image-carrying fiber bundle from the laser that focusing objective len projects.
Optionally, in order to enable the type for the fluorescent dye that the based endoscopic imaging device of the present embodiment can excite is more, selection
Range is bigger, and applicability is wider, and the laser of the present embodiment is tunable ultrashort pulse laser, using tunable ultrashort pulse
Laser, based endoscopic imaging device have the ability for realizing nonlinear imaging.Optionally, the pulse of tunable ultrashort pulse laser is wide
Degree is femtosecond magnitude, and the imaging of two-photon fluorescence service life can be achieved after focusing, improve imaging depth.Optionally, tunable ultrashort arteries and veins
The output waveband of laser is rushed in 400-1300nm, the excitation wavelength comprising a variety of fluorescent dyes.
When actually detected, if the area at position to be detected is larger, one-time detection may not be able to cover all
Position to be detected needs mobile image-carrying fiber bundle, and in order to realize the automation of detection, the based endoscopic imaging device of the present embodiment is also wrapped
Displacement control device is included, which connect with image-carrying fiber bundle and controller, has control image-carrying fiber bundle mobile
Function.Optionally, displacement control device can realize that one end of mechanical arm is connected to biography picture using existing mechanical arm configuration
On fiber optic bundle, mechanical arm is connect with controller, can drive image-carrying fiber bundle rotation or movement etc. under the control of the controller.
Optionally, controller and scanning galvanometer, laser, displacement control device and single photon counter in the present embodiment
Between be all made of coaxial cable and be attached.Certainly, the controller in the present embodiment and scanning galvanometer, laser, Bit andits control
Other feasible connection types can be used in connection between device and single photon counter, and the present embodiment is not limited in this respect.
In order to solve the above technical problems, the present embodiment proposes fluorescence based on the structure of above-mentioned based endoscopic imaging device
The acquisition methods of service life distributed image, be stored in controller in the present embodiment scanning galvanometer, laser, single photon counter with
And the control software of displacement control device.The acquisition methods of the Fluorescence lifetime distribution image are real by above-mentioned based endoscopic imaging device
Existing, referring to fig. 4, the acquisition methods of the Fluorescence lifetime distribution image of the present embodiment include:
Step 401, laser emit laser；
In the present embodiment, in order to enable Fluorescence lifetime distribution image is more acurrate, need to guarantee target area (above-mentioned example
In position to be detected) in inject fluorescent dye excitation degree, so laser transmitting laser output wavelength need
First determine.Before step 401, further includes: the excitation wavelength of the fluorescent dye of (injection or to be injected) is determined in target area,
The actual wavelength that laser is determined according to the excitation wavelength adjusts the output wavelength of laser according to the actual wavelength of the laser.
Step 402, scanning galvanometer successively scan the laser through dichroscope on the different optical fiber of image-carrying fiber bundle,
In, laser reaches the different optical fiber of image-carrying fiber bundle after scanning galvanometer injection through lens set；
In step 402, laser can be scanned galvanometer and successively scan on the different optical fiber of image-carrying fiber bundle, in same a period of time
It carves, transmission has laser on an only fiber core.
Laser is imported miniature graded index prism by step 403, image-carrying fiber bundle, to irradiate miniature graded index rib
Target area under mirror, wherein injection has fluorescent dye in target area；
Step 404, from target area issue fluorescence signal by miniature graded index prism receive after, pass sequentially through biography
As fiber optic bundle, lens set, scanning galvanometer, dichroscope and optical filter are transferred to single photon counter, wherein fluorescence signal
It is generated by fluorescent dye through laser excitation；
Step 405, single photon counter carry out photoelectric conversion according to fluorescence, and the result of conversion is sent to controller；
Step 406, controller determine fluorescent dye in the Fluorescence lifetime distribution image of target area according to the result of conversion.
Single photon counter is counted to photon and is carried out photoelectric conversion in step 405, by the knot of photoelectric conversion
Fruit is sent to controller, and controller carries out the processing such as spectrum analysis according to the result of conversion, obtains the fluorescent image of target area,
Wherein because of optical fiber interval in image-carrying fiber bundle, grid is had on the fluorescent image, controller can be calculated by gaussian filtering
Method carries out denoising, removes the grid in fluorescent image, the fluorescent image corrected using other processing.Based on glimmering
The other information that light image and/or single photon counter obtain finally obtains the Fluorescence lifetime distribution image of target area.
Optionally, the fluorescent dye of the present embodiment is to carry medicine fluorescent dye, determines fluorescent dye according to result in controller
After the Fluorescence lifetime distribution image of target area, further includes:
Controller obtains the corresponding relationship of preset Fluorescence lifetime distribution image and cell micro-environment situation；
Controller analyzes target area according to the Fluorescence lifetime distribution image and above-mentioned corresponding relationship of target area
Cell micro-environment situation；
And/or controller is released according to drug in the cell of the Fluorescence lifetime distribution map analysis target area of target area
It puts and migrates.
In one example, if target area is that a part at position to be detected is then after step 406 also wrapped
It includes:
It is to be checked that the mobile image-carrying fiber bundle of controller command displacement control device is moved to miniature graded index prism
It surveys on other regions at position and carries out above-mentioned steps 401-406 to obtain the Fluorescence lifetime distribution image of whole target areas.
Referring to Fig. 5, the present embodiment also proposes a kind of acquisition of Fluorescence lifetime distribution image based on above-mentioned based endoscopic imaging device
Method is stored with the control of scanning galvanometer, laser, single photon counter and displacement control device in the present embodiment in controller
Software processed.The acquisition methods of the Fluorescence lifetime distribution image include the following steps:
Step 501, the power supply for opening scanning galvanometer and single photon counter；
Step 502, opening controller open scanning galvanometer, tunable ultrashort pulse laser and single photon counter
Control software；
Step 503 opens tunable ultrashort pulse laser, according to the excitation wave of the fluorescent dye of affected areas injection
It is long, adjust the output wavelength of tunable ultrashort pulse laser；
Step 504, the load medicine fluorescent dye that targeting is injected to affected areas；
Step 505, control image-carrying fiber bundle are directed at affected areas to be measured, open the test key of based endoscopic imaging device；
After the test presses switch to open, tunable ultrashort pulse laser emits laser, and laser is in dichroscope, scanning vibration
Enter image-carrying fiber bundle under the action of mirror, field flattening lens, cylinder mirror and focusing objective len etc., eventually arrives at affected areas, affected areas
Fluorescent dye issue fluorescence under the excitation of laser, which is finally transferred to single photon by the structure of based endoscopic imaging device
Counter (specific transmission process is shown in the description of other embodiments, and details are not described herein)；
Step 506, single photon counter is obtained to the fluorescence signal that affected areas is excited and photoelectric conversion,
The result of conversion is transferred to controller；
Step 507, controller obtain the Fluorescence lifetime distribution figure of affected areas according to the information that single photon counter transmits
Picture, controller show Fluorescence lifetime distribution image on a display screen；
Step 508 judges whether there are also the regions that do not detect in affected areas；If so, entering step 509, otherwise, enter
Step 510；
The region that step 509, the position for adjusting image-carrying fiber bundle are not detected into affected areas, return step 506；
Step 510 obtains preset Fluorescence lifetime distribution image and cell micro-loop in existing fluorescence lifetime database
The corresponding relationship of border situation analyzes affected areas according to the corresponding relationship and the Fluorescence lifetime distribution image of affected areas
In cell micro-environment situation and affected areas in cell drug release and migration.
It, can be by fluorescence lifetime imaging technical application in clinical in situ detection, in real time in human body using the present embodiment
The region in portion carries out fluorescence lifetime detection, promotes accuracy in detection, especially generates active influence to the tentative diagnosis of cancer.
And the present embodiment uses tunable ultrashort pulse laser, the type of fluorescent dye can be excited more, range of choice is big, applicability
Extensively, and there is the ability for realizing nonlinear imaging, tunable ultrashort pulse laser is the other laser of femtosecond, it can be achieved that double light
Sub- fluorescence lifetime imaging improves imaging depth.Laser and fluorescence signal are conducted using imaging fibre, the versatility of equipment is good, can
It is in situ that internal or deep layer patient part is monitored in real time.Using scanning mode of the fiber optic bundle in conjunction with scanning galvanometer, compare
In traditional Endoscopy, resolution ratio is higher.
In several embodiments provided herein, it should be understood that disclosed device and method can pass through it
Its mode is realized.For example, the apparatus embodiments described above are merely exemplary, for example, the division of module, only
A kind of logical function partition, there may be another division manner in actual implementation, for example, multiple module or components can combine or
Person is desirably integrated into another system, or some features can be ignored or not executed.Another point, shown or discussed is mutual
Between coupling, direct-coupling or communication connection can be through some interfaces, the INDIRECT COUPLING or communication link of device or module
It connects, can be electrical property, mechanical or other forms.
Module may or may not be physically separated as illustrated by the separation member, show as module
Component may or may not be physical module, it can and it is in one place, or may be distributed over multiple networks
In module.Some or all of the modules therein can be selected to achieve the purpose of the solution of this embodiment according to the actual needs.
It should be noted that for the various method embodiments described above, describing for simplicity, therefore, it is stated as a series of
Combination of actions, but those skilled in the art should understand that, the present invention is not limited by the sequence of acts described because
According to the present invention, certain steps can use other sequences or carry out simultaneously.Secondly, those skilled in the art should also know
It knows, the embodiments described in the specification are all preferred embodiments, and related actions and modules might not all be this hair
Necessary to bright.
In the above-described embodiments, it all emphasizes particularly on different fields to the description of each embodiment, there is no the portion being described in detail in some embodiment
Point, it may refer to the associated description of other embodiments.
The above are the acquisition methods to a kind of based endoscopic imaging device provided by the present invention and Fluorescence lifetime distribution image
Description, for those skilled in the art, thought according to an embodiment of the present invention, in specific embodiments and applications
It will change, to sum up, the contents of this specification are not to be construed as limiting the invention.
Claims (10)
1. a kind of based endoscopic imaging device characterized by comprising laser transmission module interior peeps module and fluorescence lifetime imaging mould
Block；
The laser transmission module includes laser, dichroscope, scanning galvanometer and lens set, and the interior module of peeping includes passing picture
Fiber optic bundle and the miniature graded index prism connecting with the image-carrying fiber bundle, the laser that the laser issues successively pass through
The dichroscope, scanning galvanometer and lens set reach one end of the image-carrying fiber bundle, the transmission through the image-carrying fiber bundle
It is projected from the miniature graded index prism；
The fluorescence lifetime imaging module includes optical filter, the single photon counter with number of photons statistics and photoelectric conversion function
And the controller with spectrum analysis function, the optical filter be located at the dichroscope and the single photon counter it
Between, the controller is connect with the single photon counter, the laser and the scanning galvanometer, from the miniature gradual change
The light that index prism is injected successively passes through the image-carrying fiber bundle, lens set, scanning galvanometer, dichroscope and the optical filter
Reach the single photon counter.
2. based endoscopic imaging device as described in claim 1, which is characterized in that the lens set include field flattening lens, cylinder mirror and
Focusing objective len successively reaches the biography by the field flattening lens, cylinder mirror and focusing objective len by the laser of the scanning galvanometer
As fiber optic bundle.
3. based endoscopic imaging device as described in claim 1, which is characterized in that the laser that the laser issues passes through described two
To the transmission of Look mirror to the scanning galvanometer；The light injected from the miniature graded index prism successively passes through the biography
As the transmission arrival dichroscope of fiber optic bundle, lens set and scanning galvanometer, pass through institute after the reflection of the dichroscope
It states optical filter and reaches the single photon counter.
4. based endoscopic imaging device as described in claim 1, which is characterized in that the laser is tunable ultra-short pulse laser
Device.
5. based endoscopic imaging device as claimed in claim 4, which is characterized in that the pulse of the tunable ultrashort pulse laser
Width is femtosecond magnitude.
6. based endoscopic imaging device as claimed in claim 4, which is characterized in that the output of the tunable ultrashort pulse laser
Wave band is in 400-1300nm.
7. based endoscopic imaging device as claimed in any one of claims 1 to 6, which is characterized in that further include and the image-carrying fiber bundle
Connection has the function of controlling the mobile displacement control device of the image-carrying fiber bundle, the displacement control device and the control
Device connection processed.
8. based endoscopic imaging device as claimed in any one of claims 1 to 6, which is characterized in that the controller and the scanning are shaken
Coaxial cable is all made of between mirror, laser and the single photon counter to be attached.
9. a kind of acquisition methods of Fluorescence lifetime distribution image, which is characterized in that the acquisition side of the Fluorescence lifetime distribution image
Method is based on the based endoscopic imaging device of any of claims 1-8 and realizes that the Fluorescence lifetime distribution image obtains
The method is taken to include:
The laser emits laser；
The laser through the dichroscope is successively scanned the different optical fiber to the image-carrying fiber bundle by the scanning galvanometer
On, wherein the laser reaches the different optical fiber of the image-carrying fiber bundle after scanning galvanometer injection through the lens set；
The laser is imported the miniature graded index prism by the image-carrying fiber bundle, to irradiate the miniature gradient index
Target area under rate prism, wherein injection has fluorescent dye in the target area；
After the fluorescence signal issued from the target area is received by the miniature graded index prism, the biography is passed sequentially through
It is described as fiber optic bundle, lens set, scanning galvanometer, dichroscope and the optical filter are transferred to the single photon counter
Fluorescence signal is generated by the fluorescent dye through the laser excitation；
The single photon counter carries out photoelectric conversion according to the fluorescence, and the result of conversion is sent to the controller；
The controller determines the fluorescent dye in the Fluorescence lifetime distribution image of target area according to the result.
10. the acquisition methods of Fluorescence lifetime distribution image as claimed in claim 9, which is characterized in that the fluorescent dye is
Medicine fluorescent dye is carried, determines the fluorescent dye in the Fluorescence lifetime distribution of target area according to the result in the controller
After image, further includes:
The controller obtains the corresponding relationship of preset Fluorescence lifetime distribution image and cell micro-environment situation；The controller
According to the Fluorescence lifetime distribution image and the corresponding relationship of the target area, the cell micro-loop of the target area is analyzed
Border situation；
And/or the cell of controller target area according to the Fluorescence lifetime distribution image analysis of the target area
The release and migration of middle drug.
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