CN207590663U - A kind of tumor-microvessel imager - Google Patents
A kind of tumor-microvessel imager Download PDFInfo
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- CN207590663U CN207590663U CN201720502927.4U CN201720502927U CN207590663U CN 207590663 U CN207590663 U CN 207590663U CN 201720502927 U CN201720502927 U CN 201720502927U CN 207590663 U CN207590663 U CN 207590663U
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Abstract
The utility model discloses a kind of tumor-microvessel imager, including infrared co-focusing imaging part and control section;Near-infrared co-focusing imaging part includes near infrared laser, dichroscope, two-dimensional scanning mirrors, scanning lens group, image-forming objective lens, near-infrared fluorescent optical filter, convergent lens, pin hole and detector;Scanning lens group by field lens and cylinder microscope group into;Control section includes two-dimensional scan control module, signal amplification and acquisition module and the data processing image display for controlling two-dimensional scanning mirrors;Fluorescence excitation spectrum is injected in the blood vessel of organism to be seen, then the tumor section of the organism is placed under tumor-microvessel imager and is observed in 1000 to 1350nm and near-infrared quantum dots of the fluorescence emission spectrum between 1350nm to 1500nm.It realizes to the utility model energy high-resolution and Complete three-dimensional imaging is carried out to organism tumor-microvessel.
Description
Technical field
The utility model belongs to field of biomedicine technology, is related to a kind of tumor-microvessel imager more particularly to one kind
Operating wavelength range is in the Image-forming instrument of 1300 ~ 1500nm wave bands.
Background technology
The generation of tumor-microvessel has extremely important to the growth and intrusion transfer of tumour, particularly to tumour early stage
Influence, research shows that, the fast-growth of tumour especially malignant tumour relies on angiogenesis.Capilary is rich in some tumours
Richness, form is inmature, the complicated network structure, exists in composition, form and spatial distribution etc. apparent heterogeneous that is, swollen
Knurl microvascular architecture phenotype heterogeneity.This heterogeneity may be the various blood vessel lifes in the regulatory mechanism of Tumor Angiongesis
Into the unbalance of promotive factor and inhibiting factor.Between precancerous lesion and primary tumor and metastatic tumor, microvascular architecture phenotype is also deposited
In difference, the therapeutic process of another aspect anticancer drug also has a significant effect to microvascular architecture,
Therefore, if can long time-histories observation vivo tumor region capilary three-D space structure variation, will be to swollen
The occurrence and development process of knurl provides more fully objective basis, and new thinking is provided for tumour antiangiogenesis therapy
Since capilary is distributed in tumor tissues, complete structure can be in several millimeters of magnitudes, and more subtle capillary
Pipeline is about some tens of pm or so, this makes the research of the three-D space structure of capilary lack effective tool.It is clinical at present for
The imaging method of blood vessel mainly has ultrasound, CT angiographies and nuclear-magnetism angiography, however these methods are tens of micro- to differentiate
The capillary pipeline of rice is still extremely difficult.
Gradually starting to move towards the optical imaging method of clinical practice at present has the resolution ratio of micron even submicron order,
Capilary can be easily differentiated, but biological tissue is serious to scatter the imaging depth for limiting optical imaging method, even
The optical coherent chromatographic imaging and multi-photon imaging, the imaging depth reported at present for having certain depth imaging capability also can only be
1 millimeter or so.In recent years, two area's fluorescent marker of near-infrared that Stanford University Dai et al. made has reached preferable depth
Imaging effect, the possibility of the vivo observation for tumor blood vessels intact form provide theories integration.
Utility model content
In order to solve the above-mentioned technical problem, the utility model provides a kind of tumor-microvessel Image-forming instrument, can be right
Tumor vessel carries out profound imaging, draws out the three-dimensional space shape of tumor-microvessel.
Technical solution is used by the utility model:A kind of tumor-microvessel imager, it is characterised in that:Including infrared
Co-focusing imaging part and control section;The near-infrared co-focusing imaging part includes near infrared laser, dichroscope, two
Tie up scanning galvanometer, scanning lens group, image-forming objective lens, near-infrared fluorescent optical filter, convergent lens, pin hole and detector;It is described to sweep
Retouch lens group by field lens and cylinder microscope group into;
The control section include for control the two-dimensional scanning mirrors two-dimensional scan control module, signal amplification with
Acquisition module and data processing image display;
The near infrared light that the near infrared laser is sent out is reflected into the two-dimensional scan by the dichroscope and shakes
Enter the field lens after mirror, the plane of scanning motion formed at told field lens focal plane, later by the cylinder mirror it is parallel be incident on it is described
Image-forming objective lens simultaneously assemble the plane of scanning motion to form sample plane in sample stage, scan biological sample;The near-infrared that sample is excited
Fluorescence is parallel after being collected by the image-forming objective lens to become directional light after cylinder mirror convergence by the field lens, using institute
It states projection after two-dimensional scanning mirrors move back scanning and passes through the dichroscope, by the near-infrared fluorescent optical filter, then it is described
Convergent lens is focused to a bit, which enters the detector after penetrating the pin hole;The signal of detector output is through the letter
The data processing image display, which is sent into, after number amplification and acquisition module carries out signal processing.
The utility model is based on biological tissue in 2nd area of near-infrared(1300nm~1500nm)Absorb less, scattering less with it is spontaneous
The characteristics of fluorescence is low, with reference to the ability of the tomography of conjugate focus imaging technique, and with near-infrared quantum dots marked tumor blood vessel,
It is imaged so as to fulfill to the three-dimensional structure of tumor-microvessel.Near-infrared quantum dots exciting light and transmitting light is utilized all close near red
The characteristics of outer 2nd area, preferably laser wavelength range 1000nm ~ 1350nm near-infrared laser excitation emission spectra 1300nm ~
Two area's quantum dot of near-infrared of 1500nm, so as to fulfill tumor vascular deep layer living imaging, obtains the three-dimensional of tumor-microvessel
Intact form.
Description of the drawings
Fig. 1 is the structure diagram of the utility model embodiment;
In figure, 1- near infrared lasers, 2- two-dimensional scan control modules, 3- two-dimensional scanning mirrors, 4- field lenses, 5- mirrors,
6- image-forming objective lens, 7- sample stages, 8- dichroscopes, 9- near-infrared fluorescent optical filters, 10- convergent lenses, 11- pin holes, 12- detections
Device, the amplification of 13- signals and acquisition module, 14- data processing image displays.
Specific embodiment
It is clear in order to be more clear the purpose of this utility model, technical solution and advantage, below in conjunction with attached drawing and implementation
Example, the present invention is further described in detail, it should be appreciated that specific embodiment described herein is only used to explain
The utility model is not used to limit the utility model, in addition, involved in each embodiment of the utility model described below
And to technical characteristic can be combined with each other as long as they do not conflict with each other.
Referring to Fig.1, a kind of tumor-microvessel imager provided by the utility model, including infrared co-focusing imaging part and
Control section;Near-infrared co-focusing imaging part includes near infrared laser 1, dichroscope 8, two-dimensional scanning mirrors 3, scanning thoroughly
Microscope group, image-forming objective lens 6, near-infrared fluorescent optical filter 9, convergent lens 10, pin hole 11 and detector 12;Scanning lens group is by field lens
4 and cylinder mirror 5 form;Control section include for control two-dimensional scanning mirrors 3 two-dimensional scan control module 2, signal amplification with
Acquisition module 13 and data processing image display 14;
The near infrared light that near infrared laser 1 is sent out is reflected into 3 laggard admission of two-dimensional scanning mirrors by dichroscope 8
Mirror 4 forms the plane of scanning motion at told 4 focal plane of field lens, is incident on image-forming objective lens 6 and in sample stage 7 by cylinder mirror 5 is parallel later
The plane of scanning motion for forming sample plane is assembled, scans biological sample;The near-infrared fluorescent that sample is excited is collected by image-forming objective lens 6
It is parallel afterwards to become directional light by field lens 4 after the convergence of cylinder mirror 5, project process after moving back scanning using two-dimensional scanning mirrors 3
Dichroscope 8 by near-infrared fluorescent optical filter 9, then is converged lens 10 and is focused to a bit, which enters after penetrating pin hole 11
Detector 12;The signal that detector 12 exports is through signal amplification with being sent into data processing image display 14 after acquisition module 13
Carry out signal processing.
In order to obtain good imaging effect, aforementioned each optical device should have preferable transmitance in designated wavelength range
Or reflectivity, detector have preferable response curve.Specific features are as follows:
It is semiconductor pumped solid that 1 operation wavelength of near infrared laser should be 1000 ~ 1350nm, preferably 1064nm or 1310nm
Body laser.
Dichroscope 8 is using the light reflectivity > 90% for being less than 1350nm to wavelength, to wavelength 1350nm ~ 1500nm's
Light transmission rate is more than 90% long pass filter.
Two-dimensional scanning mirrors 3 are more than 90% to the light reflectivity of wavelength 1000nm ~ 1600nm.
Field lens 4, cylinder mirror 5, image-forming objective lens 6 and convergent lens 10 are more than the light transmission rate of wavelength 1000nm ~ 1600nm
90%, 6 operating distance > 10mm of image-forming objective lens, numerical aperture are more than 0.2.
Near-infrared fluorescent optical filter 9 is more than 90%, and to cutoff wavelength OD to the light transmission rate of wavelength 1400nm ~ 1500nm
Bandpass filter more than 3.
Pin hole 11 should be located at the focal plane of convergent lens 10, and size is the Airy size of convergent lens 10.
Detector 12 should abut pin hole and place, and should use the photomultiplier of indium gallium arsenic material.
The near-infrared quantum dots that fluorescence emission wavelengths are 1300nm ~ 1500nm should be filled in the blood vessel of biological sample.
The utility model can be used for carrying out image acquisition to the individual layer section of tumor-microvessel, implement process
It is:
It is swollen that the biological sample for being marked with the near-infrared quantum dots that fluorescence emission wavelengths are 1300nm ~ 1500nm is placed in this
Under knurl blood vessel imaging instrument, the near infrared light that near infrared laser 1 is sent out is reflected into two-dimensional scanning mirrors 3 by dichroscope 8
Enter field lens 4 afterwards, the plane of scanning motion is formed at 4 focal plane of field lens, is incident on image-forming objective lens 6 and in sample by cylinder mirror 5 is parallel later
Sample platform 7 assembles the plane of scanning motion for forming sample plane.The near-infrared fluorescent that sample is excited parallel warp after being collected by image-forming objective lens 6
It crosses after cylinder mirror 5 is assembled and becomes directional light by field lens 4, projection is by dichroscope after moving back scanning using two-dimensional scanning mirrors 3
8, it by near-infrared fluorescent optical filter 9, then is converged lens 10 and is focused to a bit, which enters detector after penetrating pin hole 11
12;The signal that detector 12 exports inputs to data processing image display after being acquired by signal amplification with acquisition module 13
14, the signal that point by point scanning detects is converted into the gray value of single pixel by data processing image display 14, by its sequence
Single layer image is obtained after arrangement, the individual layer cross-section diagram of tumor-microvessel can be obtained in this way.
The utility model can be used for the three-dimensional structure image acquisition to tumor-microvessel, and specific implementation process is:
It is swollen that the biological sample for being marked with the near-infrared quantum dots that fluorescence emission wavelengths are 1300nm ~ 1500nm is placed in this
Under knurl blood vessel imaging instrument, the near infrared light that near infrared laser 1 is sent out is reflected into two-dimensional scanning mirrors 3 by dichroscope 8
Enter field lens 4 afterwards, the plane of scanning motion is formed at 4 focal plane of field lens, is incident on image-forming objective lens 6 and in sample by cylinder mirror 5 is parallel later
Sample platform 7 assembles the plane of scanning motion for forming sample plane.The near-infrared fluorescent that sample is excited parallel warp after being collected by image-forming objective lens 6
It crosses after cylinder mirror 5 is assembled and becomes directional light by field lens 4, projection is by dichroscope after moving back scanning using two-dimensional scanning mirrors 3
8, it by near-infrared fluorescent optical filter 9, then is converged lens 10 and is focused to a bit, which enters detector after penetrating pin hole 11
12;The signal that detector 12 exports inputs to data processing image display after being acquired by signal amplification with acquisition module 13
14, the signal that point by point scanning detects is converted into the gray value of single pixel by data processing image display 14, by its sequence
Single layer image is obtained after arrangement, then sample stage 7 rise certain altitude, preferably 5um, repeat the above process can obtain it is next
The single layer image of layer, so recycles certain number of plies, preferably 1000 layers, these sequence images are carried out three-dimensional reconstruction can be swollen
The three-dimensional structure image of knurl capilary.
Although this specification has more used near infrared laser 1, two-dimensional scan control module 2, two-dimensional scanning mirrors
3rd, field lens 4, cylinder mirror 5, image-forming objective lens 6, sample stage 7, dichroscope 8, near-infrared fluorescent optical filter 9, convergent lens 10, pin hole 11
With detector 12, signal amplification and the terms such as acquisition module 13 and data processing image display 14, but use is not precluded
The possibility of other terms.The use of these items is only for more easily describing the essence of the utility model, they are solved
It is all contrary to the spirit of the present invention to be interpreted into any one of the additional limitations.
By fluorescence excitation spectrum 1000 to the near-infrared of 1350nm and fluorescence emission spectrum between 1350nm to 1500nm
Quantum dot is injected in the blood vessel of organism to be seen, then by the tumor section of the organism be placed under tumor-microvessel imager into
Row observation.It realizes to the utility model energy high-resolution and Complete three-dimensional imaging is carried out to organism tumor-microvessel.
It should be understood that the part that this specification does not elaborate belongs to the prior art.
It should be understood that the above-mentioned description for preferred embodiment is more detailed, can not therefore be considered to this
The limitation of utility model patent protection domain, those of ordinary skill in the art are not departing under the enlightenment of the utility model
Under the ambit that the utility model claims are protected, replacement or deformation can also be made, each falls within the utility model
Within protection domain, the utility model is claimed range and should be determined by the appended claims.
Claims (8)
1. a kind of tumor-microvessel imager, it is characterised in that:Including near-infrared co-focusing imaging part and control section;
The near-infrared co-focusing imaging part includes near infrared laser(1), dichroscope(8), two-dimensional scanning mirrors(3)、
Scanning lens group, image-forming objective lens(6), near-infrared fluorescent optical filter(9), convergent lens(10), pin hole(11)And detector(12);
The scanning lens group is by field lens(4)With cylinder mirror(5)Composition;
The control section includes controlling the two-dimensional scanning mirrors(3)Two-dimensional scan control module(2), signal amplification
With acquisition module(13)With data processing image display(14);
The near infrared laser(1)The near infrared light sent out passes through the dichroscope(8)It is reflected into the two-dimensional scan
Galvanometer(3)Enter the field lens afterwards(4), in told field lens(4)The plane of scanning motion is formed at focal plane, later by the cylinder mirror(5)
It is parallel to be incident on the image-forming objective lens(6)And in sample stage(7)The plane of scanning motion for forming sample plane is assembled, scans biological sample
This;The near-infrared fluorescent that sample is excited is by the image-forming objective lens(6)It is parallel after collection to pass through the cylinder mirror(5)After convergence by
The field lens(4)Become directional light, using the two-dimensional scanning mirrors(3)The dichroscope is passed through in projection after moving back scanning
(8), by the near-infrared fluorescent optical filter(9), then by the convergent lens(10)It is focused to a bit, which penetrates the needle
Hole(11)Enter the detector afterwards(12);Detector(12)The signal of output amplifies through the signal and acquisition module(13)Afterwards
It is sent into the data processing image display(14)Carry out signal processing.
2. tumor-microvessel imager according to claim 1, it is characterised in that:The near infrared laser(1)Work
Wavelength should be 1000 ~ 1350nm.
3. tumor-microvessel imager according to claim 1, it is characterised in that:The dichroscope(8)Using to wave
The long light reflectivity > 90% less than 1350nm leads to optical filtering to wavelength in length of the light transmission rate of 1350nm ~ 1500nm more than 90%
Piece.
4. tumor-microvessel imager according to claim 1, it is characterised in that:The two-dimensional scanning mirrors(3)To wave
The light reflectivity of long 1000nm ~ 1600nm is more than 90%.
5. tumor-microvessel imager according to claim 1, it is characterised in that:The field lens(4), cylinder mirror(5), imaging
Object lens(6)And convergent lens(10)90% is more than to the light transmission rate of wavelength 1000nm ~ 1600nm;The image-forming objective lens(6)Work
Distance > 10mm, numerical aperture are more than 0.2.
6. tumor-microvessel imager according to claim 1, it is characterised in that:The near-infrared fluorescent optical filter(9)
It is more than 90% for the light transmission rate to wavelength 1400nm ~ 1500nm, and is more than 3 bandpass filter to cutoff wavelength OD.
7. tumor-microvessel imager according to claim 1, it is characterised in that:The pin hole(11)Positioned at convergent lens
(10)Focal plane at, size be convergent lens(10)Airy size;The detector(12)Against pin hole(11)It places,
And the photomultiplier of indium gallium arsenic material should be used.
8. according to the tumor-microvessel imager described in claim 1-7 any one, it is characterised in that:The biological sample
The near-infrared quantum dots for there are fluorescence emission wavelengths to be 1300nm ~ 1500nm are filled in blood vessel in advance.
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