CN107290319A - A kind of detection method and its application of autofluorescence distribution and intensity based on lung tissue - Google Patents
A kind of detection method and its application of autofluorescence distribution and intensity based on lung tissue Download PDFInfo
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- CN107290319A CN107290319A CN201710556519.1A CN201710556519A CN107290319A CN 107290319 A CN107290319 A CN 107290319A CN 201710556519 A CN201710556519 A CN 201710556519A CN 107290319 A CN107290319 A CN 107290319A
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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
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6402—Atomic fluorescence; Laser induced fluorescence
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/62—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light
- G01N21/63—Systems in which the material investigated is excited whereby it emits light or causes a change in wavelength of the incident light optically excited
- G01N21/64—Fluorescence; Phosphorescence
- G01N21/6486—Measuring fluorescence of biological material, e.g. DNA, RNA, cells
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Abstract
The invention provides the autofluorescence distribution based on lung tissue and the detection method of intensity, comprise the following steps:(1) detection lung tissue is under the exciting of the 700nm exciting lights of single photon 400 or the 1000nm exciting lights of two-photon 700, and the wavelength sent is 420 800nm autofluorescence;(2) in comparison step (1) each position of lung tissue autofluorescence intensity and distributional pattern, and the autofluorescence in step (1) and the autofluorescence distributional pattern and intensity results of known early stage or Patients with Advanced Lung Cancer and non-lung cancer crowd are contrasted;(3) judge that cancerous lung tissue is in early stage or late period according to above-mentioned comparing result:It is compared with the early stage of lung cancer that lung's fluorescence structure, which is reunited,;Dimmed lung's fluorescence is then relatively late lung cancer.The present invention establishes a kind of autofluorescence based on lung tissue and judges the method that lung cancer is in early stage or late period.
Description
Technical field
The present invention relates to the biological autofluorescence of detection cancerous lung tissue, specifically based on detection lung tissue autofluorescence distribution shape
State changes and intensity is reduced, and the method and its application in early stage or late period are in as detection lung cancer.
Background technology
It is also China's morbidity and mortality highest malignant tumour in world wide that lung cancer, which is, and it has grade malignancy
High, progress is fast, weak curative effect the features such as.For a people for occurring lung cancer presumptive signs first, carrying out a rabat detection can carry
The problems such as showing obvious agglomerate, the expansion of mediastinum film, atelectasis.CT images are can to provide more disease informations.Bronchoscope
Inspection and CT are often used to extract tumor sample for histopathological analysis judgement.On rabat, it is seen that lung tumors one
As be solitary pulmonary nodule form.However, because many other diseases also have secondary feature, including hamartoma, infectiousness granulation
Knurl etc..So also needing further diagnosis.For lung cancer, conclusive diagnosis is the lump sample for taking suspected tumor, utilizes group
Pathological method is knitted to judge.Clinical practice guideline suggestion is periodically checked Lung neoplasm.But CT is due to its radiation hazradial bundle,
It is not recommended that high-frequency or using for a long time.
The lung cancer of relatively early stage can be clinically detected using CT image technologies at present, if tumour very little, 5 annual survival rates can
With more than 80%.But major problem is that, majority of populations does not have the custom of periodic detection lung cancer.CT images are not easy to simultaneously
Everybody detects.And the detection method for lung cancer is only limitted to these image methods, and cough at present, expiratory dyspnea, hemoptysis, entirely
The apparent rough judgement such as body fat-reducing and apocleisis.It is very inconvenient for patient, take relatively long and price costly.To disease
People quickly non-invasively judges that early stage or advanced lung cancer have important clinical meaning.And after surgery in order to judge that it is early that lung cancer is in
Phase or late period, for the pathologic finding generally several days time of resection organization.Therefore, cut for patient lung and by operation
The lung tissue removed, if it is possible to invention can easy, the quick detection lung cancer method that is in early stage or late period, this will have weight
Big social and economic significance and clinical value.
The content of the invention
The purpose of the present inventor is to break through the problem of prior art, proposes that one kind can be used for live body and detect in real time at lung cancer
In novel detection method and the application in early stage or late period.
Present invention discover that the distributional pattern of the tissue autofluorescence of the relatively early stage of lung cancer focal area of patients with lung cancer is presented and reunited
Shape.Net distribution with normal lung tissue autofluorescence is significantly different.Relatively late tumour autofluorescence intensity is substantially less than normally
The cancerous lung tissue of lung tissue and relatively early stage.This method finds occur aggregating state in lung tissue's specific wavelength autofluorescence form
Or intensity reduces, the judgement symbol in early stage or late period is in as lung cancer.
Based on this discovery, detection method and instrument that clinically quick diagnosis lung cancer is in early stage or late period can also be set up
Device.
The present invention concrete technical scheme be:
A kind of detection method of autofluorescence distribution and intensity based on lung tissue, comprises the following steps:
(1) light irradiation detected person's lung is excited with single photon 400-700nm exciting lights or two-photon 700-1000nm
Portion is organized, to inspire the autofluorescence of the lung tissue.
(2) autofluorescence intensity of the wavelength that detection lung tissue sends in the range of 420-800nm;
(3) in comparison step (2) each position of lung tissue autofluorescence distributional pattern and intensity;
(4) and by the autofluorescence intensity of step (2) and known early and late patients with lung cancer, the lung of non-lung cancer crowd
Tissue autofluorescence distributional pattern and intensity results are contrasted;
(5) according to above-mentioned comparing result, complete be based on lung tissue autofluorescence judge lung cancer be in early days or
The detection method in late period.The wavelength that lung tissue is sent is 420-800nm autofluorescence luminous intensities, and lung's autofluorescence presents netted
Structure for normal structure;It is compared with the early stage of lung cancer that agglomeration, which occurs, in lung's autofluorescence;Lung's autofluorescence is significantly reduced, and is
Relatively late lung cancer.
Further, the mode of the utilization excitation lung tissue autofluorescence is defeated including the use of common continuous light
In the mode for go out the mode excited, the mode that excites being modulated using electrical modulation or is excited using pulse laser
At least one.
Further, the lung tissue can directly be detected with live body, can also be in vitro pattern detection.
Further, lung's autofluorescence present network structure for normal structure;Reuniting now occurs in lung's autofluorescence
As for compared with the early stage of lung cancer;The more significant reduction of lung's autofluorescence is then relatively late lung cancer.
Further, the wavelength of the exciting light is:Single photon 400-700nm exciting lights or two-photon 700-
1000nm。
Further, the wavelength of the autofluorescence is in the range of 420-800nm.
Judge that lung cancer is in the method in early stage or late period present invention also offers a kind of autofluorescence based on lung tissue
Using.
The present invention is reduced using the distribution and intensity for detecting lung tissue's autofluorescence, judges that lung cancer is in early stage or evening
Phase, it is that clinical judgment lung cancer is in early stage or late period sets up basis, can greatly reduces diagnosing and be in early stage or late period
Time.According to this method and principle, corresponding Medical Instruments or device can be manufactured.
Brief description of the drawings
Fig. 1:Exciting light 488nm excites sample lung tissue autofluorescence, receiver wavelength range 500-530nm reception light.
Autofluorescence changes figure.
Fig. 2:Exciting light 640nm excites sample lung tissue autofluorescence, receiver wavelength range 650-700nm reception light.
Autofluorescence changes figure.
Fig. 3:Exciting light 488nm excites sample lung tissue autofluorescence, receiver wavelength range 500-530nm reception light.
Autofluorescence changes figure.
Fig. 4:Exciting light 640nm excites sample lung tissue autofluorescence, receiver wavelength range 650-700nm reception light.
Autofluorescence changes figure.
Embodiment
Below will be by specifically describing, the present invention is further illustrated.
Unless otherwise defined, all technologies used herein and scientific terminology have and the technical field of the invention
Those of ordinary skill be generally understood that identical implication.
The term " autofluorescence " used in the present invention, its implication is that biomolecule is being excited light irradiation by appropriate wavelength
When, the energy for absorbing exciting light enters excitation state, then exits excitation state to launch showing for the light longer than excitation wavelength
As in, the longer light of the wavelength ratio excitation wavelength.
The term " exciting light " used in the present invention, its implication is that biomolecule can be excited to occur autofluorescence phenomenon
Light, its wavelength should be shorter than autofluorescence.
Inventor has carried out a series of experiments, it is determined that the distribution and intensity of lung tissue's autofluorescence reduce and lung cancer
Relation between early stage or late period.
First, experimental method:
Early and late lung cancer patient or non-lung cancer patient lung tissue are taken, using laser confocal microscope to lung
Tissue samples carry out real time imagery.
2nd, experimental result and discussion
Fig. 1:Exciting light 488nm excites sample lung tissue autofluorescence, receiver wavelength range 500-530nm reception light.
Compared with the early stage of lung cancer lung's autofluorescence compared with normal lung tissue autofluorescence, in form occur fluorescence agglomeration.
Fig. 2:Exciting light 640nm excites sample lung tissue autofluorescence, receiver wavelength range 650-700nm reception light.
Compared with the early stage of lung cancer, compared with normal lung tissue autofluorescence fluorescence agglomeration occurs for lung's autofluorescence in form.
Fig. 3:Exciting light 488nm excites sample lung tissue autofluorescence, receiver wavelength range 500-530nm reception light.
Lung's autofluorescence of relatively late lung cancer is compared with normal lung tissue autofluorescence, fluorescence intensity reduction.
Fig. 4:Exciting light 640nm excites sample lung tissue autofluorescence, receiver wavelength range 650-700nm reception light.
Lung's autofluorescence of relatively late lung cancer is compared with normal lung tissue autofluorescence, fluorescence intensity reduction.
Being tested more than to draw, lung autofluorescence present network structure for normal structure;Lung's autofluorescence occurs
Agglomeration is compared with infantile tumour;Lung's autofluorescence reduction is then relatively late tumour.
The present invention is based on this discovery, establishes a kind of method that live body real-time judge lung cancer is in early stage or late period.Side
Method comprises the following steps:
(1) light irradiation detected person's lung is excited with single photon 400-700nm exciting lights or two-photon 700-1000nm
Portion is organized, to inspire the autofluorescence of the lung tissue.
(2) autofluorescence intensity of the wavelength that detection lung tissue sends in the range of 420-800nm;
(3) in comparison step (2) each position of lung tissue autofluorescence distributional pattern and intensity;
(4) and by patients with lung cancer and the non-lung cancer crowd of the autofluorescence intensity of step (2) and known early stage or late period
Lung tissue's autofluorescence distributional pattern and intensity results contrasted;
(5) according to above-mentioned comparing result, the autofluorescence for completing to be based on lung tissue judges that lung cancer is in early stage or evening
The detection method of phase.What network structure was presented in lung's autofluorescence that the wavelength that lung tissue is sent is 420-800nm is normal
Tissue;It is compared with infantile tumour that agglomeration, which occurs, in lung's autofluorescence;It is then relatively late tumour that lung's autofluorescence, which is significantly reduced,.
The mode using the subcutaneous autofluorescence of excitation of the present invention is carried out including the use of common continuous light output
In the mode that excites, the mode that the mode that excites is modulated using electrical modulation or is excited using pulse laser at least
It is a kind of.
In the detection method of the present invention, in the range of the wavelength of exciting light is preferably 420-680nm, more preferably 460-
In the range of 643nm.
It is more excellent in the range of the wavelength of the autofluorescence detected is preferably 440-750nm in the detection method of the present invention
In the range of electing 450-741nm as.
The live body of the present invention examines the method that lung cancer is in early stage or late period in real time, according to lung tissue's autofluorescence distributional pattern
With the testing result of the change of intensity, judge to be in early stage or late period by the lung cancer of experimental subjects.Further rule is, lung
Autofluorescence present network structure for normal structure;It is compared with the early stage of lung cancer that agglomeration, which occurs, in lung's autofluorescence;Lung's autofluorescence
Reduction is then relatively late lung cancer.
It should be understood that the live body of the present invention detects that lung cancer is in the implementation of the method in early stage or late period and disobeyed in real time
Rely in detection device.Any equipment that can be sent exciting light and autofluorescence can be detected can be used to implement this
The live body of invention detects the method that lung cancer is in early stage or late period in real time.
Although those skilled in the art is it should be understood that for illustrative purposes, this document describes the tool of the present invention
Body embodiment, but various modifications can be carried out to it without departing from the spirit and scope of the present invention.Therefore, it is of the invention specific
Embodiment and embodiment should not be considered as limiting the scope of the invention.The present invention is limited only by the appended claims.This Shen
Please in quote all documents be fully incorporated herein by reference.
The invention discloses one kind based on detection lung tissue's autofluorescence distribution and intensity as detection lung cancer at
In detection method and its application in early stage or late period.This method finds to reunite in lung tissue's specific wavelength autofluorescence form
State is the early stage of lung cancer, or lung tissue's specific wavelength autofluorescence intensity is substantially reduced as advanced lung cancer.Present invention firstly provides
Judge that lung cancer is in the methods and applications in early stage or late period with lung tissue's autofluorescence distribution and intensity.At the judgement lung cancer
In the detection method of early stage or late period it is easy, in real time, can be in Clinical practice.
Claims (7)
1. a kind of detection method of autofluorescence distribution and intensity based on lung tissue, comprises the following steps:
(1) light irradiation detected person lung group is excited with single photon 400-700nm exciting lights or two-photon 700-1000nm
Knit or surgery excision lung tissue, to inspire the autofluorescence of the lung tissue;
(2) the autofluorescence distributional pattern and intensity of wavelength that the lung tissue sends in the range of 420-800nm are detected;
(3) in comparison step (2) each position of lung tissue autofluorescence distributional pattern and intensity;
(4) and by the autofluorescence intensity of step (2) and known early and late patients with lung cancer and the lung of non-lung cancer crowd
Tissue autofluorescence distributional pattern and intensity results are contrasted;
(5) according to above-mentioned comparing result, the detection method that the autofluorescence based on lung tissue judges lung cancer is completed.
2. the method as described in claim 1, it is characterised in that:
The mode using excitation lung tissue autofluorescence is excited including the use of common continuous light output
Mode, at least one of the mode excited or the mode excited using pulse laser are modulated using electrical modulation.
3. the method as described in claim 1, it is characterised in that the tissue and organ are:Thymus gland, lymph node.
4. the method as described in claim 1, it is characterised in that:
The tissue can directly be detected or in vitro pattern detection with live body.
5. the method as described in claim 1, it is characterised in that:
Malignant solid tumor autofluorescence is substantially less than the autofluorescence of malignant solid tumor correspondence normal structure.
6. the method as described in claim 1, it is characterised in that:
Lung's autofluorescence present network structure for normal structure;There is agglomeration for the early stage of lung cancer in lung's autofluorescence;
It is then advanced lung cancer that lung's autofluorescence, which is significantly reduced,.
7. the conduct detection lung cancer of a kind of autofluorescence distribution and intensity based on lung tissue is in early stage or late period mark
The application of will.
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Cited By (2)
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CN110068681A (en) * | 2018-01-24 | 2019-07-30 | 上海交通大学 | A kind of Novel marker predicted or detect lung cancer |
CN110432862A (en) * | 2018-05-04 | 2019-11-12 | 上海交通大学 | Based on many places sites spontaneous fluorescence intensity variation comprehensive analysis with judge distinguish lung cancer and cerebral apoplexy method and its application |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN110068681A (en) * | 2018-01-24 | 2019-07-30 | 上海交通大学 | A kind of Novel marker predicted or detect lung cancer |
CN110432862A (en) * | 2018-05-04 | 2019-11-12 | 上海交通大学 | Based on many places sites spontaneous fluorescence intensity variation comprehensive analysis with judge distinguish lung cancer and cerebral apoplexy method and its application |
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