CN202184721U - Lymph gland and blood vessel upper conversion fluorescent imaging system - Google Patents
Lymph gland and blood vessel upper conversion fluorescent imaging system Download PDFInfo
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- CN202184721U CN202184721U CN2011201750577U CN201120175057U CN202184721U CN 202184721 U CN202184721 U CN 202184721U CN 2011201750577 U CN2011201750577 U CN 2011201750577U CN 201120175057 U CN201120175057 U CN 201120175057U CN 202184721 U CN202184721 U CN 202184721U
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Abstract
The utility model discloses a lymph gland and blood vessel upper conversion fluorescent imaging system, which comprises a semiconductor laser device, an upper conversion fluorescent detector and a computer system. The semiconductor laser device projects laser to a detected substance via laser fiber groups and stimulates the detected substance to generate fluorescent light, the upper conversion fluorescent detector receives fluorescent light, converts the fluorescent light into digital signals, and transmits the digital signals into the computer system via a signal transmission circuit, and the computer system processes the digital signals and realizes imaging. The lymph gland and blood vessel upper conversion fluorescent imaging system can realize real-time and safe imaging for lymph glands marked by upper conversion fluorescent nanometer materials, and provides a new method for high-efficiently, accurately and safely positioning the lymph glands and studying relevant lesion of blood vessels.
Description
Technical field
This utility model relates to biological tissue's technical field of imaging, relates in particular to a kind of lymph node and blood vessel up-conversion fluorescence imaging system.
Background technology
Lymphsystem is an ingredient of vascular system, is made up of lymph pipelines at different levels, lymphatic organ and the lymphoid tissue that is dispersed in.Lymphsystem is not only participated in body fluid circulation and lipid metabolism, also has hemopoietic and immunologic function, is one of system of defense of wanting of body weight for humans, and is closely related with multiple diseases such as allergy, obesity, infection, diabetes and tumors.The lymph node imaging technique is the important channel of studying the lymphsystem function and in disease, acting on, and particularly in diagnosing tumor treatment and relapse and metastasis, especially comes into one's own.
Sentinel node (sentinel lymph node SLN) is meant in the primary tumo(u)r lymphatic drainage zone, lymph metastasis must through the first stop lymph node, it can be used as barrier and temporarily stops tumor cell in lymphoid further diffusion.In clinical operation treatment, the surgeon is among a small circle operation in advance often, attempts to find and first stop lymph node that the tumor resection lymphatic drainage arrives, checks it and is invaded state, and whether decision goes large-scale lymph cleaning art again.The SLN state is the important evidence whether diagnosing tumour spreads and determine therapeutic scheme; SLN biopsy feminine gender can be avoided the unnecessary expansion of performing the operation; The misery that can alleviate the patient with improve the quality of living, so the proposition of SLN biopsy notion is landmark progress in the surgical oncology field.Find that as early as possible sentinel node has or not transfer for the clinical stages of tumor and take the corresponding treatment measure and appropriate modus operandi all has significance.At present, SLN biopsy technology has become the standard art formula of melanoma and breast carcinoma, and is generalized to gradually in the diagnosis and treatment of gastric cancer, colorectal cancer, carcinoma of prostate, cervical cancer, carcinoma of endometrium, carcinoma vulvae and tumor of head and neck.
How accurately to find SLN, promptly SLN being positioned is the key technology of SLN biopsy.The lymph node imaging technique is the localized method of a kind of SLN, helps and finds SLN in the Rhizoma Atractylodis Macrocephalae as early as possible.At present clinical method commonly used has three kinds: (1) dyestuff tracer method just can make lymphatic vessel, lymph node painted in the bio-active dye number such as injection methylene blue minute in the art.This method is tradition comparatively, and is simple and easy to do, but needs the doctor that long learning curve is arranged.Blindly, consuming time many in the art when selecting skin incision, damage is big, and mostly dyestuff be micromolecule, just drains into next stage lymph node in several minutes in drain to the SLN, with the accuracy that influences the SLN biopsy.(2) isotopic tagging method, isotope 99mTc commonly used can pass through the strongest lymph node of located irradiation property to confirm SLN.This method advantage clear and definite location before Rhizoma Atractylodis Macrocephalae, it is with strong points perform the operation, damage for a short time, but because of existing radioactive pollution to endanger the generation of patient and medical personnel's health, and apparatus expensive, has limited its clinical practice.(3) dyestuff and radionuclide associating tracer method, this method are the methods of reliable localization SLN the most so far.
The continuous development of nanometer new material also provides more method for the lymph node imaging.People such as Kim utilize near-infrared II type fluorescence quantum that the axillary fossa SLN of mice and pig is positioned imaging.Through being expelled to the fluorescence that the intravital quantum dot of toy sends, can be at the external SLN that observes directly the axillary fossa place.This fluorescence signal is strong and stable, need not operation, so quantum dot animal fluorescence imaging technology is opened new situation for clinical SLN location.But quantum dot contains heavy metal cadmium (Cd), has very strong bio-toxicity; Even,, still have the Cd ion in vivo in the environment and ooze out like SiO2 through finishing parcel organic polymer or inorganic material; Build up toxigenicity, thereby limited the interior application prospect of body of quantum dot.
Recently, (Up-converting Phosphor, UCP) application in bio-imaging has caused the concern of more and more researcheres to up-conversion luminescent material.Traditional fluorescent material is luminous all to be met Stokes' law (Stokes ' law), promptly generally always greater than exciting light wavelength, luminous in other words photon energy is less than the energy of excitation photon to the emission wavelength of luminescent material usually.And up-conversion luminescence is a kind of at the infrared ray excited luminescence phenomenon that sends visible light down; Be characterized in that the photon energy that is absorbed is lower than the photon energy of being launched; Promptly convert long-wave radiation to shortwave radiation through multi-photon mechanism, this phenomenon is called the anti-Stokes effect.Adopt near-infrared as exciting light, organize lessly, luminous reflectance or the scattering generation background fluorescence that yet can not be excited can not take place, thereby greatly improve the sensitivity that forms images light absorption.The luminescence phenomenon of UCP is the pure physical process that results from inside configuration, and fluorescence has high stability, is difficult for cancellation.Simultaneously, compare UCP nanoparticle good biocompatibility, no cytotoxicity with quantum dot.Therefore; If up-conversion luminescent material is applied to the lymph node imaging technique; Develop and a kind of novel lymph node formation method and system; Be expected to solve some problems that existing method exists, for the surgical oncology operative treatment provides more effectively, more accurate, safer lymph node detects and positioning means.
Summary of the invention
This utility model technical problem to be solved is; Limitation and deficiency to existing above-mentioned lymph node formation method; Adopt the up-conversion fluorescence nano material as lymph node imaging and angiographic label, a kind of lymph node imaging and blood vessel up-conversion fluorescence imaging system are provided.
A kind of lymph node and blood vessel imaging up-conversion fluorescence imaging system is characterized in that, comprising:
Semiconductor laser, through the laser fiber group with laser projections to surveying thing, excite and survey deposits yields fluorescence;
The up-conversion fluorescence detector receives fluorescence and converts digital signal into, transfers to computer system through signal transmission line;
Computer system is handled digital signal, imaging.
Said up-conversion fluorescence detector comprises lens barrel; Be provided with optical filter group, optical lens group, ccd image sensor in the lens barrel; Automatically detect and adjust the control circuit of optical lens group focal length; The laser fiber group penetrates the lens barrel interior and extends to the lens barrel front end from lens barrel tail end end, described lens barrel front end end face be provided with the laser fiber group in laser fiber optical fiber outlet one to one.
Described laser fiber group comprises 4 laser fibers, and described optical fiber export volume is 4, and 4 optical fiber outlet uniform ring distribute around the lens barrel axis.
The laser fiber that is protected penetrates the axis of the partial parallel lens barrel of lens barrel interior.
It is the semiconductor laser of 980nm that said semiconductor laser adopts centre wavelength.
Wherein, the described up-conversion fluorescence nano material rare earth ion doped up-conversion fluorescence nanoparticle (NaYF that is
4: Yb, Ln (Ln=Er
3+, Tm
3+, Ho
3+, Pr
3+, Nd
3+)), the water solublity up-conversion nanoparticles particle diameter that is used for the labelling lymph node is generally 20~30nm.
The up-conversion fluorescence detector is through its positive four optical fiber outlet emission 980nm near-infrared excitation light; Form even, symmetric irradiation and excite scope; Survey thing and place the scope center that excites, up-conversion fluorescence particle wherein is stimulated institute's emitted fluorescence through after the reflection of optical filter group and filtering, and amplifies adjustment through battery of lens; On ccd image sensor, form images, and convert digital signal into through control circuit and transmit.The optical filter group can reflect scattered light and the selective permeation emission light of 980nm, specifically filters wavelength and selects according to the particle emission spectrum that is adopted.
This utility model is compared with existing lymph node imaging technique, has the following advantages:
1. traditional dyestuff tracer technique is a color identification method owing to what adopt, and strong through the perusal subjectivity, sensitivity is low; Compare with luminescent detection techniques, the latter is through the ccd image sensor detection of photons, through computer Recognition; Sensitivity and accuracy all improve a lot; Adopt up-converting phosphor technology and system,, can obtain the more image-forming information of position, deep because 980nm near infrared light penetrate tissue ability is stronger.
2 with isotopic tagging method and quantum dot imaging location relatively, there is not heavy metallic poison in the radiological hazard that this utility model has existed when having avoided adopting radionuclide to position yet, good biocompatibility, suitable biomarker and detection.
3. the up-conversion fluorescence nano material owing to labelling lymph node in this utility model is excited by the stable state near infrared laser; Tissue is less to the absorption of light; Luminous reflectance or the scattering generation background fluorescence that yet can not be excited can not take place; Thereby greatly improving imaging sensitivity, is a kind of high-sensitive imaging technique.
4. upconverting fluorescent material excites hardly by photobleaching at the stable state near-infrared laser, and is little to body injury, so this utility model is a kind of imaging technique that can carry out in real time lymph node, observe continuously.
Description of drawings
Fig. 1 is the structural representation of this utility model system;
Fig. 2 is this utility model up-conversion fluorescence panel detector structure sketch map;
Fig. 3 is the test pattern of detector shown in Figure 2;
Fig. 4 is a detector A-A profile shown in Figure 2.
The specific embodiment
As shown in Figure 1; Change the fluorescence imaging system on a kind of lymph node and the blood vessel; Be made up of up-conversion fluorescence detector A, signal transmission line C, laser fiber group D, computer system E, semiconductor laser F, it is the semiconductor laser of 980nm that semiconductor laser F adopts centre wavelength, and the laser that it sends is projected to through laser fiber group D and surveys thing B; Surveying thing B changes fluorescent material because injection has to go up; After exciting, can produce fluorescence, up-conversion fluorescence detector A receives to survey the fluorescence that thing B sent and convert digital signal into and transfers on the computer system E through signal transmission line C and handle, and finally is embodied as picture.
Up-conversion fluorescence detector A comprises lens barrel 14; Be provided with optical filter group 1, optical lens group 2, highly sensitive ccd image sensor 3 in the lens barrel 14; Automatically detect and adjust the control circuit of optical lens group 2 focal lengths; The laser fiber group comprises four optical fiber 8~11, and every optical fiber penetrates lens barrel 14 interior and extends to lens barrel 14 front ends from lens barrel 14 tail end ends, the parallel lens barrel axis of laser fiber.Lens barrel 14 front end end faces are provided with 4 and laser fiber optical fiber outlet one to one 4~7, and optical fiber outlet 4~7 uniform ring distribute around the lens barrel axis, and the lens barrel tail end also is provided with laser fiber group D and signal transmssion line way outlet 13, is convenient in the sets of lines.
With the synthetic water solublity up-conversion nanoparticles NaYF of institute
4: Yb
0.18, Ho
0.02(Φ=20~30nm) are centrifugal, and deposition is resuspended in (37 ℃ of vibration 30min) in the PBS solution, and the ultimate density of gained lymph node labelling injection solution is 4.5mg ml
-1, pH value is 7.4.
Normal New Zealand large ear rabbit (8 ages in week are about 2kg) as experimental animal, anaesthetize by 30mg/kg, strikes off the hind leg chaeta, gets the ventricumbent position by 2% sodium pentobarbital solution.Extract 500 μ l lymph node labelling injection with the 1ml syringe, at hind leg far-end claw inserting needle, soft massage injection site behind the subcutaneous injection.Injection back 5-10 minute, F shines in the kneed face muscular prominence fossa part in the wrong of hind leg position with semiconductor laser (centre wavelength is 980nm), gathers fluorescence signal with portable up-conversion fluorescence detector A.
Result:, expose the faint yellow lymph node that rouge nest rear intramuscular is surveyed the position, i.e. rouge nest lymph node in the position row topography of the kneed face muscular prominence fossa part in the wrong of rabbit hind leg.Under the 980nm laser irradiation, rouge nest place lymph node detects strong green fluorescence signal, and obvious with the surrounding tissue contrast, its downstream lymphatic vessel also can blur-free imaging.
With the synthetic water solublity up-conversion nanoparticles NaYF of institute
4: Yb
0.18, Ho
0.02(Φ=20~30nm) are centrifugal, and deposition is resuspended in (37 ℃ of vibration 30min) in the PBS solution, and ultimate density is 4.5mg ml
-1, pH value is 7.4.
Normal New Zealand large ear rabbit (8 ages in week are about 2kg) is as experimental animal.Blood vessel is clamped with the large size mosquito forceps in rabbit ear middle, to prevent venous return, injection NaYF
4: Yb
0.18, Ho
0.02The PBS solution 200ul of nanoparticle is in the ear vein blood vessel, and F shines at the intravascular injection position with semiconductor laser (centre wavelength is 980nm), gathers fluorescence signal with portable up-conversion fluorescence detector A.
Result: under natural lighting; Can find out that the prominence is a rabbit ear vein, surperficial fur is coarse, is covered with fine hair; If adopt common exciting light to shine; Hair can produce very strong reflection and autofluorescence, adopts up-conversion nanoparticles to be carried out to the generation that picture can effectively be avoided autofluorescence, and observed from different perspectives rabbit ear vein has vessel branch clearly.
Claims (5)
1. lymph node and blood vessel up-conversion fluorescence imaging system is characterized in that, comprising:
Semiconductor laser (F), through laser fiber group (D) with laser projections to surveying thing (B), excite and survey thing (B) and produce fluorescence;
Up-conversion fluorescence detector (A) receives fluorescence and converts digital signal into, transfers to computer system (E) through signal transmission line (C);
Computer system is handled digital signal, imaging.
2. lymph node according to claim 1 and blood vessel up-conversion fluorescence imaging system; It is characterized in that; Said up-conversion fluorescence detector (A) comprises lens barrel; Be provided with optical filter group (1), optical lens group (2), ccd image sensor (3) in the lens barrel; Automatically detect and the control circuit of adjustment optical lens group (2) focal length, the laser fiber group penetrates the lens barrel interior and extends to the lens barrel front end from lens barrel tail end end, described lens barrel front end end face be provided with the laser fiber group in laser fiber optical fiber outlet one to one.
3. lymph node according to claim 2 and blood vessel up-conversion fluorescence imaging system are characterised in that described laser fiber group comprises 4 laser fibers, and described optical fiber export volume is 4, and 4 optical fiber outlet uniform ring distribute around the lens barrel axis.
4. lymph node according to claim 2 and blood vessel up-conversion fluorescence imaging system is characterized in that the laser fiber that is protected penetrates the axis of the partial parallel lens barrel of lens barrel interior.
5. lymph node according to claim 1 and blood vessel up-conversion fluorescence imaging system is characterized in that, it is the semiconductor laser of 980nm that said semiconductor laser (F) adopts centre wavelength.
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102871651A (en) * | 2012-10-26 | 2013-01-16 | 哈尔滨海鸿基业科技发展有限公司 | Near infrared lymphatic detector |
CN105547516A (en) * | 2016-01-07 | 2016-05-04 | 复旦大学 | Laser pumped up-conversion fluorescence temperature measurement system |
CN108498079A (en) * | 2018-05-08 | 2018-09-07 | 翰飞骏德(北京)医疗科技有限公司 | Recognition methods and the equipment of glimmering Control of Environment Pollution by Light medium vessels, lymphatic vessel and lymph node |
CN112617753A (en) * | 2020-12-17 | 2021-04-09 | 湖南马尼克医疗科技有限公司 | Transmission-type fluorescence radiography equipment capable of detecting deep lymphatic vessels and lymph nodes |
CN113331242A (en) * | 2021-05-19 | 2021-09-03 | 曹海平 | Whole convertible two-sided detection pork lymph remove device |
CN113349707A (en) * | 2013-12-31 | 2021-09-07 | 纪念斯隆-凯特琳癌症中心 | System, method and apparatus for real-time multi-channel imaging of fluorescence sources |
CN113905659A (en) * | 2019-02-04 | 2022-01-07 | 麻省理工学院 | System and method for lymph node and blood vessel imaging |
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2011
- 2011-05-27 CN CN2011201750577U patent/CN202184721U/en not_active Expired - Fee Related
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102871651A (en) * | 2012-10-26 | 2013-01-16 | 哈尔滨海鸿基业科技发展有限公司 | Near infrared lymphatic detector |
CN113349707A (en) * | 2013-12-31 | 2021-09-07 | 纪念斯隆-凯特琳癌症中心 | System, method and apparatus for real-time multi-channel imaging of fluorescence sources |
CN105547516A (en) * | 2016-01-07 | 2016-05-04 | 复旦大学 | Laser pumped up-conversion fluorescence temperature measurement system |
CN105547516B (en) * | 2016-01-07 | 2019-11-12 | 复旦大学 | Laser pump (ing) up-conversion fluorescence temp measuring system |
CN108498079A (en) * | 2018-05-08 | 2018-09-07 | 翰飞骏德(北京)医疗科技有限公司 | Recognition methods and the equipment of glimmering Control of Environment Pollution by Light medium vessels, lymphatic vessel and lymph node |
CN113905659A (en) * | 2019-02-04 | 2022-01-07 | 麻省理工学院 | System and method for lymph node and blood vessel imaging |
CN112617753A (en) * | 2020-12-17 | 2021-04-09 | 湖南马尼克医疗科技有限公司 | Transmission-type fluorescence radiography equipment capable of detecting deep lymphatic vessels and lymph nodes |
CN113331242A (en) * | 2021-05-19 | 2021-09-03 | 曹海平 | Whole convertible two-sided detection pork lymph remove device |
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