CN109078268A - The accurate lung field irradiation unit of radiobiological experiment magazine-type mouse - Google Patents

The accurate lung field irradiation unit of radiobiological experiment magazine-type mouse Download PDF

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Publication number
CN109078268A
CN109078268A CN201810654022.8A CN201810654022A CN109078268A CN 109078268 A CN109078268 A CN 109078268A CN 201810654022 A CN201810654022 A CN 201810654022A CN 109078268 A CN109078268 A CN 109078268A
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mouse
slot
sliding block
irradiation unit
lung field
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周成
张鹏
陈明
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Zhejiang Cancer Hospital
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Zhejiang Cancer Hospital
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00Radiation therapy
    • A61N5/10X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Pathology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Radiation-Therapy Devices (AREA)

Abstract

The present invention provides a kind of accurate lung field irradiation unit of radiobiological experiment magazine-type mouse, it is made of bracket mainboard, bottom plate, two sets of clip structures, upper gas nozzle and lower gas nozzle, bracket mainboard is vertical with bottom plate at 90 degree of right angles, 2 sets of card holder structures are distributed in from top to bottom on bracket mainboard, and card holder structure is mainly lacked by wedge, sliding block, U slot, block board, card holder foot are constituted.The present invention integrates anesthesia, fixation, positioning, whole noninvasive gas anesthesia, it is ensured that depth of anesthesia and eupnea alleviate workload, reduce the risk of injury mouse body, to avoid head member as the exposure for radiating most sensitive position.Apparatus of the present invention design is reasonable, easy to operate, safe, and environmental protection, fixed effect is obvious, and thoracic cavity positions clamping structure deft design, accurate positioning, and the mouse suitable for not of the same age section may be implemented in fixed non-displacement.Practicability and versatility are all relatively strong, are a kind of accurate irradiation field utensils of efficient animal irradiation.

Description

The accurate lung field irradiation unit of radiobiological experiment magazine-type mouse
Technical field
The invention belongs to experiment appliances, are related to a kind of test mouse device more particularly to a kind of radiobiological experiment The accurate lung field irradiation unit of magazine-type mouse.
Background technique
Mouse radiation pneumonitis experimental model is research radioactivity organ damage, respiratory disease and immune response mechanism Important tool, have irreplaceable value in fields such as radioecology, radiotherapeutics, anti-injury of lungs medicament research and developments. Induced lung injury early stage is mainly shown as radiation pneumonitis (usual secondary radiotherapy after the 1-3 month), due to a large amount of T lymphocytes by Immune response, a kind of lymphatic pulmonary alveolitis are generated to activation;Advanced stage can develop as interstitial pulmonary fibrosis (after irradiation 6 months or so).Once it is serious dysfunction of ventilation or respiratory failure that its consequence, which occurs, for pulmonary fibrosis, cause chronic pulmonary therewith Property heart disease in source eventually leads to the vicious circle of cardio-pulmonary function obstacle (cardiopulmonary syndrome).Pulmonary fibrosis is still lacked at present effectively Class of medications.
On the other hand, induced lung injury animal model is not only having for research early stage radiation pnuemonitis and dose of radiation relationship With tool, also change process with very much like chronic inflammation and fibrillatable pathological because of it, while being also research idiopathic lung The ideal model of fibrosis (idiopathic pulmonary fibrosis, IPF) pathogenesis.
However, there is no objective, noninvasive, the quantitative Diagnosis technology for radioactivity murine pneumonia model at present both at home and abroad.? In recent decades experimental study, tested after still quantifying irradiation using a variety of invasive and/or noninvasive technology in the world Mouse lung toxic reaction, including lethality, respiratory rate or lung compliance, Histological change, and with high resolution ct and Micro-CT carrys out testing and evaluation radiotoxicity effect.It is lacked however, these models or check and evaluation method still have many technologies It falls into.
First, physiologic parameters (i.e. respiratory rate, lung compliance, lethality or weight) can more objective reaction lung limit Abnormal gas caused by property dysfunction of ventilation processed, diffusivity interstitial inflammation or scar exchanges, but these parameters be easy by it is many other The interference of factor, such as temperature, infection, merging cardiac toxic.
Second, using can only be in lung tissue section it is observed that a small amount of pneumonia, these physiologic index when low dose exposure Lesion degree is relatively light or the self-healing stage can not actual response pulmonary lesion: also do not observe apparent respiratory rate change, Individual death or weight loss (when such as x-ray dosage < 10.5Gy), are easy to appear false negative situation.However this false negative situation, Graded doses (from low to high) measured value is usually required in mathematical physics modeling and carries out operation and simulation, i.e. low dose group detects Value sensitivity will directly affect the accuracy and reliability of model.
Third, since lung function has larger compensatory capacity, the assessment for early stage injury of lungs (i.e. inflammation phase), tissue Learn interstitial lung thicken that evidence, inflammatory cell hyperplasia or infiltration and individual mice be dead or respiratory rate increase have no it is directly related Property, this influences the accuracy of result to a certain extent.
4th, from statistical angle, these methods measurement acquisition data belong to ordinal number variable (ordinal data) Or quantitative response data (graded response data), before carrying out Probit or Logistic model analysis, it is necessary to root It factually tests animal number amount and carries out quantization reaction (quantal response) conversion.This usually requires that test different experiments every time Group is required to keep sizable initial sample size, it is especially desirable in view of the radioactive poison side effect of middle and advanced stage is (as seriously put Penetrating property dermatitis) and the individual death that dramatically increases of high dose group.
5th, although noninvasive high resolution ct or micro-CT have some superiority on identifying advanced stage lung fiber, this Advantage is generated dependent on excessive collagen albumen and cicatrization.And radiation pneumonitis does not have the change of this fibrosis, because This is only difficult to realize the detection to mouse initial lung inflammation with high resolution ct or micro-CT image itself.In addition, radioactivity Injury of lungs is closely related with dose of radiation, and risk caused by additional x-ray dose commitment caused by long-term CT follow-up can not be ignored.One As CT picture noise (noise propagation) and (dosage Dose)-1/2(Pixel Dimensions isotropic voxel size)-2It is directly proportional.In CT image, every n times of the raising of intrinsic resolution, the dose of radiation that mouse receives needs to improve this meaning n4Times.Briefly, it needs to transport to reduce image motion artifact (such as breathing, heartbeat) in micro-CT or high-resolution ct With relatively long sweep time and respiratory gating technology, for the x-ray dosage of scanning exposure up to 100-300mGy, this will be straight every time Connect interference radiation dosetest.
Summary of the invention
The purpose of the present invention is overcoming the shortcomings of the prior art and technical bottleneck, a kind of radiobiological experiment is provided The accurate lung field irradiation unit of magazine-type mouse,
Apparatus of the present invention are made of, bracket bracket mainboard 1,2, two sets of clip structures 3 of bottom plate, upper gas nozzle 4 and lower gas nozzle 5 Mainboard 1 is vertical with bottom plate 2 at 90 degree of right angles, it is ensured that load-bearing and structural stability, bracket mainboard 1 are distributed two independences from top to bottom Functional unit, i.e. 2 sets of card holder structures 3,3 surface of card holder structure is block board 6, and 10 wedges are evenly distributed on block board 6 and lack 7 (for the groove of wedge) lacks upper 5 (the mouse head of gas nozzle 4 and lower gas nozzle of the corresponding configuration of 7 top 1:1 for accommodating mouse thoracic cavity, wedge Portion's anaesthetic mask), wedge lacks 7 mouthfuls of ends and places 10 sliding blocks 8 respectively, lacks in 7 to fixed mouse in wedge, 8 inside of sliding block is (close Mouse side) coated with sponge become foaming structure, it is ensured that and entire fixation procedure mouse is unlikely to occur skin, internal organ because pressure is excessive It squeezes and is damaged, while also not influencing the dynamic degree of mouse eupnea, be adjustable structure on the outside of sliding block 8, by sliding block screw hole 14 and slide 15 two parts of block screw are constituted, and can carry out individuation fine tuning, 10 adjustable sliding blocks 8 according to mouse difference thoracic cavity size It is all positioned in U slot 12, carrier of the U slot 12 as sliding block 8,12 left-hand end of U slot is placed in by fixed screw (not shown) It is used as rotation center on left side detent hand 11, allows to rotating horizontally 180 degree, facilitates the filling and irradiation of mouse after anesthesia The release of mouse afterwards, 12 right-hand end of U slot is movable and is fixed on right side detent hand 11 by U slot screw 9 and U slot screw hole 10.
2, two sets of bracket mainboard 1, bottom plate 3 constituent apparatus main bodys of clip structure, using polymethyl methacrylate materials (Poly-methylmethacrylat), can avoid scattering after x-ray is injected and cause mouse absorbed dose error, at the same its density with Biological tissue's ingredient is similar, convenient for radiation physics Rapid Dose Calculation.
Apparatus of the present invention are that a kind of can realize for the first time integrates anesthesia, fixation, positioning " magazine-type " mouse lung field photograph Injection device can dramatically increase accuracy, simplification, safety, stability and the high efficiency of breast radiation experiment.Substantially lower real Test cost and while the time, decrease dependence to IGRT toy irradiation instrument, by routine clinical accelerator energy Carry out the full lung field irradiation of high-precision, high-volume mouse.The component utilizes existing natural anatomic after the flat upper act of the double upper limbs of mouse Structure exposes thoracic cavity with complete to firm;Gathered using clamp compression, the principle of moving rotary card slot, aptamer limit, will be divided It Shi Xian not fix, brake the function of limit and radiation positioning.Present invention uses multinomial technological innovation, design science, effect is bright It is aobvious.Maximum bright spot is: matched 1:1 invasive ventilation anaesthetic mask is used in combination in 1. apparatus of the present invention, whole Noninvasive gas anesthesia, it is ensured that depth of anesthesia and eupnea;2. being designed using elastic force fixing bolt, suitable for not of the same age section of difference The experiment mice of figure;3. using mouse humerus and thoracic cavity fixed design, completes the braking to whole mouse and limit, alleviate work Amount reduces the risk of injury mouse body;4. the design of card holder structure increases irradiation safety: mouse upper limb and this jail of above section Jail control is more than fixed frame, it is ensured that neck and head position relatively fixed and apart from irradiation field have certain safety away from From to avoid head member as the exposure for radiating most sensitive position;5. having laser rays by medical accelerator It is wild that location fit therapeutic bed high precision adjusts the ray cloth based on the present apparatus;6. can be with different manufacturers, different types of doctor Radiometric is completed with linear accelerator is compatible.Apparatus of the present invention design is reasonable, easy to operate, safe, environmental protection, and fixed effect is bright Aobvious, thoracic cavity positions clamping structure deft design, accurate positioning, and the mouse suitable for not of the same age section may be implemented in fixed non-displacement.It is real It is all relatively strong with property and versatility, it is a kind of accurate irradiation field utensil of efficient animal irradiation.
Detailed description of the invention
Fig. 1 is schematic structural diagram of the device of the invention.
Fig. 2 separate functional unit: card holder structure structural schematic diagram.
The unadjustable fixed cell of Fig. 3: rotatable U slot structure schematic diagram.
Fixed cell: slide block structure schematic diagram is adjusted in Fig. 4.
Fig. 5 mouse lung field irradiates size and effect diagram.
Fig. 6 mouse lung field irradiates the upper bound, middle line, lower bound anatomical position CT imaging schematic diagram.
Specific embodiment
The present invention is further described in conjunction with the accompanying drawings and embodiments.
The 1 accurate lung field irradiation unit of radiobiological experiment magazine-type mouse of embodiment
Referring to Fig.1, which is made of bracket mainboard 1, bottom plate 2, card holder structure 3, upper gas nozzle 4, lower gas nozzle 5, the present invention Apparatus main body is that 2 independent card holder structures 3 form, and is one-to-one upper 4 He of gas nozzle right above upper and lower 2 sets of card holder structures 3 Lower gas nozzle 5 provides gas anesthesia agent (such as Isoflurane) with whole in irradiation process with positioning, it is ensured that mouse anesthesia in irradiation process Well, Breathing movement uniformly, skeletal muscle relative relaxation, reduce because breathing is uneven, displacement caused by not deep etc. reasons of anesthesia to Lower the accuracy of irradiation experiment.
Referring to Fig. 2, each card holder structure 3 forms (every row can be with 10 mouse of receiving) by 10 basic units side by side, Including fixed cell and anesthesia oxygen supply unit two parts.Fixed cell, as the term suggests it is to provide and tie up to fixed mouse position Most accurate mouse irradiation posture is held, 7 wedges including designing according to mouse anatomic dimensions lack, and it is flat poly- just to accommodate double forelimbs Later thoracic cavity size is placed in 6 or less block board.Wedge lacks 7 mouthfuls of ends and places 10 sliding blocks 8 respectively, to fixed mouse in contract Shape lacks in 7.
3 surface of card holder structure is block board 6, and 10 wedges are evenly distributed on block board 6 and lack 7 (wedge grooves) for accommodating Mouse thoracic cavity, 2 row's wedges lack the upper gas nozzle 4 of the corresponding configuration of 7 top 1:1 and lower gas nozzle 5 (mouse head anaesthetic mask), wedge lack 7 10 sliding blocks 8 are placed at mouth end respectively, are lacked in 7 to fixed mouse in wedge, 8 inside (nearly mouse side) of sliding block becomes coated with sponge Foaming structure, it is ensured that entire fixation procedure mouse is unlikely to occur skin because pressure is excessive, internal organ squeeze impaired, while also not shadow The dynamic degree of mouse eupnea is rung, is adjustable structure on the outside of sliding block 8, is made of sliding block screw hole 14 and 15 two parts of sliding block screw, Individuation fine tuning can be carried out according to mouse difference thoracic cavity size, 10 adjustable sliding blocks 8 are all positioned in U slot 12, U slot 12 As the carrier of sliding block 8,12 left-hand end of U slot is placed on left side detent hand 11 by fixed screw (not shown) as rotation Center allows to rotating horizontally 180 degree, facilitates the release of mouse after the filling and irradiation of mouse after anaesthetizing, 12 right side of U slot It holds movable, and right side detent hand 11 is fixed on by U slot screw 9 and 10 activity of U slot screw hole.
Referring to Fig. 3, before mouse loads, the U slot 12 for being loaded with slide block structure 8 is in release position (i.e. U slot 12 and detent Angle >=90 degree of plate 6), with facilitate by after anesthesia mouse transfer, be placed in wedge lack 7 in.After mouse placement is appropriate, rotation Reset U slot 12 (i.e. U slot 12 and 6 angle of block board are 0 degree);U slot screw 9 is inserted into the fixed spiral shell of U slot in U slot fixation hole 16 immediately Hole 10.Unadjustable fixed cell is smoothly closed, and mouse is tentatively fixed in card holder structure 3.
Referring to Fig. 4, after the completion of mouse is filled, tentatively fixes, since Individual Size is poor between there is mouse to a certain extent It is different, any adjusting of individuation can be carried out by 10 slide block structures 8 loaded respectively on U slot 12.8 inside of slide block structure is (close Mouse side) it is foaming structure coated with sponge, it is adjustable structure on the outside of slide block structure 8, is that tiny spring is supported among interior outside Structure, it is ensured that entire fixation procedure mouse is unlikely to occur skin because pressure is excessive, internal organ squeeze impaired, while also not influencing small The dynamic degree of mouse eupnea.Outside is that adjustable structure is made of sliding block screw hole 14 and 15 two parts of sliding block screw, can be according to mouse Different thoracic cavity sizes carry out individuation fine tuning.When individual mice is less than normal, sliding block screw 15 is slightly tightened inwardly;Work as mouse When individual size is bigger than normal, sliding block screw 15 can be loosened outward, discharge more spaces.
Referring to Fig. 5, after the completion of mouse is fixed, thoracic cavity position smoothly exposes immediately, draws in face of linear accelerator line Position allows ray vertically to penetrate lung field.Range of exposures and Breathing movement be consideration first in the full lung field irradiation of mouse because Element.Determine mouse lung structure in Coronal and sagittal first in iconography level by computed tomography (CT equipment) technology Anatomical position and size on bit image.And it usually and in the case of deep anaesthesia is exhaled according to mouse breathing frequency and amplitude determination The pulmonary position and size dynamic for inhaling dynamic degree image change rule.Ensure Ji Baoquan lung dynamic range when mouse receives irradiation, Adjacent organ toxicity, such as liver, stomach and intestinal tube are not increased again.
Referring to Fig. 6, further analyzed according to CT faultage image, determined respectively lung's range of exposures upper bound include apex pulmonis, Middle line and and inferior boundary of lung, and by the above Radiological measurement size with the formal notation of scale in specially design lung field irradiation dress It sets, for instructing laser rays to position and practical operation.Practical irradiation field range is on CT Coronal and sagittal image as schemed institute Show.
In conclusion induced lung injury mouse model is for a long time in pulmonary fibrosis mechanism, radioecology and anti- The fields such as clinical research are widely used before injury of lungs drug.However, can not be kept away since irradiation technique, equipment and mode are different Exempt from the inhomogeneity for leading to experimental data between different experiments room, also causes certain obstacle for horizontal comparative research.It is irradiated The various actual states such as exposure range, fixed form, anesthesia duration and depth are limited in journey, so that mouse model of lung injury exists Fail to form accurate, efficient, inexpensive standardized instrument always in irradiation link.It is " simple that the present invention realizes a kind of mouse Filling ", the thoracic cavity irradiation of " magazine-type " fix and position device, can carry out high-volume mouse by conventional medical accelerator and shine Experiment is penetrated, there is stronger research application and actual promotional value.
Embodiment 2
Carried out using 8-10 week old C57BL6 female mice model using magazine-type mouse lung field irradiation unit of the invention Accurate lung exposure experiment, specific method are described below
1. mouse is placed into the induction box full of isoflurane atomization gas before irradiation, noninvasive gas induced anesthesia is implemented;
2. mouse deep anaesthesia is transferred to the dedicated chest irradiation device of this researching and designing and properly fixes, thoracic cavity keep with Therapeutic bed is parallel;
3. irradiation unit main body uses polymethyl methacrylate materials (Poly-methylmethacrylat), can avoid X-ray causes mouse absorbed dose error after scattering after injecting;
4. device is furnished with 1:1 Atomized anesthetic gas mask, it is ensured that every mouse obtains atomization mixing isoflurane gas, Reaching anesthesia and Muscle relaxation ensures that irradiation experiment is gone on smoothly;
5. chest irradiation device can once accommodate 20 mouse simultaneously while carry out full lung irradiation experiment, but also can basis Different experiments require to further increase slot quantity to expand mouse irradiation scale.
6. being irradiated using radiotherapy department routine clinac, exposure dose can require freely according to different experiments Setting adjustment;The compatible commercialization clinacs all on the market of the present apparatus;
7. irradiation finishes, SPF grades of animal feeding rooms are sent back to, compare to later analysis.If you need to (multiple) irradiation of hyperfractionated, weight Multiple above procedure.

Claims (4)

1. a kind of accurate lung field irradiation unit of radiobiological experiment magazine-type mouse, which is characterized in that by bracket mainboard (1), Bottom plate (2), 2 sets of clip structures (3), gas nozzle (4) and lower gas nozzle (5) are constituted, and bracket mainboard (1) is vertical with bottom plate (2) at 90 degree Right angle, 2 sets of card holder structures (3) are distributed in from top to bottom on bracket mainboard (1), and card holder structure (3) surface is block board (6), card It is evenly distributed 10 wedges on position plate (6) and lacks (7), 1:1 is corresponding above each wedge scarce (7) configures upper gas nozzle (4) and lower gas nozzle (5), wedge lacks (7) mouth end and places 10 sliding blocks (8) respectively, and sliding block (8) is placed in U slot (12).
2. the accurate lung field irradiation unit of a kind of radiobiological experiment magazine-type mouse according to claim 1, feature It is, U slot (12) is the carrier of sliding block (8), and U slot (12) left-hand end is placed in conduct on left side detent hand (11) by fixed screw Rotation center facilitates horizontal rotation 180 degree, and U slot (12) right-hand end is movable and passes through U slot screw (9) and U slot screw hole (10) It is fixed on right side detent hand (11).
3. the accurate lung field irradiation unit of a kind of radiobiological experiment magazine-type mouse according to claim 1, feature Be, become foaming structure coated with sponge on the inside of sliding block (8), be adjustable structure on the outside of sliding block (8), by sliding block screw hole (14) with Sliding block screw (15) two parts are constituted, and 10 adjustable sliding blocks (8) are all positioned in U slot (12).
4. the accurate lung field irradiation unit of a kind of radiobiological experiment magazine-type mouse according to claim 1, feature It is, bracket mainboard (1), bottom plate (2), two sets of clip structure (3) constituent apparatus main bodys, using polymethyl methacrylate material Material.
CN201810654022.8A 2018-06-22 2018-06-22 The accurate lung field irradiation unit of radiobiological experiment magazine-type mouse Pending CN109078268A (en)

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CN112402814B (en) * 2020-11-12 2022-07-12 中国人民解放军海军军医大学 Fixed shielding device and method for local irradiation of batch animal ionizing radiation with adjustable target area

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