WO2020211583A1 - 中子捕获治疗系统 - Google Patents
中子捕获治疗系统 Download PDFInfo
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- WO2020211583A1 WO2020211583A1 PCT/CN2020/079731 CN2020079731W WO2020211583A1 WO 2020211583 A1 WO2020211583 A1 WO 2020211583A1 CN 2020079731 W CN2020079731 W CN 2020079731W WO 2020211583 A1 WO2020211583 A1 WO 2020211583A1
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Classifications
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- A61N5/1064—Monitoring, verifying, controlling systems and methods for adjusting radiation treatment in response to monitoring
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- G—PHYSICS
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- G21G4/02—Neutron sources
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- G—PHYSICS
- G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
- G21K—TECHNIQUES FOR HANDLING PARTICLES OR IONISING RADIATION NOT OTHERWISE PROVIDED FOR; IRRADIATION DEVICES; GAMMA RAY OR X-RAY MICROSCOPES
- G21K1/00—Arrangements for handling particles or ionising radiation, e.g. focusing or moderating
- G21K1/02—Arrangements for handling particles or ionising radiation, e.g. focusing or moderating using diaphragms, collimators
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- G—PHYSICS
- G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
- G21K—TECHNIQUES FOR HANDLING PARTICLES OR IONISING RADIATION NOT OTHERWISE PROVIDED FOR; IRRADIATION DEVICES; GAMMA RAY OR X-RAY MICROSCOPES
- G21K5/00—Irradiation devices
- G21K5/02—Irradiation devices having no beam-forming means
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- A61N2005/1092—Details
- A61N2005/1095—Elements inserted into the radiation path within the system, e.g. filters or wedges
Definitions
- the invention relates to a radiation irradiation system, in particular to a neutron capture treatment system.
- radiotherapy such as cobalt sixty, linear accelerator, and electron beam has become one of the main methods of cancer treatment.
- traditional photon or electron therapy is limited by the physical conditions of radiation itself. While killing tumor cells, it will also cause damage to a large number of normal tissues along the beam path.
- traditional radiotherapy For the more radiation-resistant malignant tumors (such as: glioblastoma multiforme, melanoma), the treatment effect is often poor.
- neutron capture therapy is a combination of the above two concepts, such as boron neutron capture therapy, through the specific accumulation of boron-containing drugs in tumor cells, combined with precise neutron beam regulation, to provide better than traditional radiation Cancer treatment options.
- BNCT Boron Neutron Capture Therapy
- 10 B boron-containing drugs
- 10 B (n, ⁇ ) 7 Li neutron capture and nuclear fission reaction Two heavily charged particles, 4 He and 7 Li, are produced. 1 and 2, which respectively show the schematic diagram of the boron neutron capture reaction and the 10 B(n, ⁇ ) 7 Li neutron capture nuclear reaction equation.
- the average energy of the two charged particles is about 2.33 MeV, which has high linearity Transfer (Linear Energy Transfer, LET), short-range characteristics, the linear energy transfer and range of alpha particles are 150keV/ ⁇ m, 8 ⁇ m, and 7 Li heavy-load particles are 175keV/ ⁇ m, 5 ⁇ m, the total range of the two particles is approximately equivalent to The size of a cell, so the radiation damage caused to organisms can be limited to the cell level.
- boron-containing drugs are selectively aggregated in tumor cells, with an appropriate neutron source, they can not cause too much damage to normal tissues. Under the premise, the purpose of locally killing tumor cells is achieved.
- boron neutron capture therapy depends on the concentration of boron-containing drugs and the number of thermal neutrons at the tumor cell location, it is also called binary cancer therapy. It can be seen that, in addition to the development of boron-containing drugs, The improvement of neutron source flux and quality plays an important role in the research of boron neutron capture therapy.
- a neutron capture treatment system including a neutron generation device and a beam shaping body
- the neutron generation device includes an accelerator and a target, so The charged particle beam generated by the accelerator and the target interact to generate neutrons, the neutrons form a neutron beam, the neutron beam defines a main axis
- the beam shaping body includes a retarder and a reflector And a radiation shield
- the retarder decelerates the neutrons generated from the target to the superthermal neutron energy zone
- the reflector surrounds the retarder and guides the neutrons deviated from the main axis back To the main axis to increase the intensity of the superthermal neutron beam
- the radiation shield is used to shield the leaking neutrons and photons to reduce the normal tissue dose in the non-irradiated area
- the beam shaping body further includes accommodating the buffer Speed body frame.
- the frame forms positioning and support for the retarder, which can improve the flux and quality of the
- the retarder is adjustable, and the frame includes a positioning member and a stop member for fixing the retarder.
- the half-life of the radioisotope generated by the materials of the positioning member and the stop member is less than 7 days after being activated by neutrons.
- the materials of the positioning member and the stop member are aluminum alloy, titanium alloy, lead-antimony alloy, cobalt-free steel, carbon fiber, PEEK or high molecular polymer.
- the positioning member can conveniently adjust the size of the retarder body, thereby adjusting the neutron beam flux, and the stop member can quickly and conveniently realize the packaging of the retarder body after adjustment.
- the retarder body includes a basic part and a supplementary part, the basic part and the supplementary part have different materials, the frame forms at least one accommodating unit, and the accommodating unit includes a first accommodating unit and a second accommodating unit adjacent to each other.
- the basic part is accommodated in the first accommodating unit and is adjustable in slices.
- the positioning member is provided in the first accommodating unit to supplement, The stop member is used to fix the basic part.
- the supplementary part can reduce the manufacturing cost of the retarder, and at the same time, will not have a greater impact on the beam quality; the positioning member and the stop member can easily adjust the basic part of the retarder.
- the frame includes a main frame and a secondary frame that are detachably connected, the first accommodating unit is formed by being surrounded by at least a part of the main frame, and the second accommodating unit is formed by at least a part of the main frame and At least a part of the secondary frame is surrounded and formed, the supplementary part is accommodated in the second accommodating unit, and the arrangement of the secondary frame facilitates replacement of the supplementary part of the retarder.
- the material of the main frame is aluminum alloy, which has good mechanical properties and has a short half-life of radioisotopes generated after being activated by neutrons; preferably, the material of the sub-frame is carbon fiber composite material, which is activated by neutrons.
- the material of the basic part includes at least one of D 2 O, Al, AlF 3 , MgF 2 , CaF 2 , LiF, Li 2 CO 3 or Al 2 O 3 , which has a large interaction cross-section with fast neutrons, The superthermal neutron action cross section is small and has a better retardation effect; the basic part contains Li-6, and the basic part simultaneously serves as the thermal neutron absorber.
- the material of the supplementary part includes at least one of Zn, Mg, Al, Pb, Ti, La, Zr, Bi, and C. The material of the supplementary part is easily available, which can reduce the manufacturing cost of the retarder. At the same time, it has a certain neutron slowing effect, which will not have a big impact on the beam quality.
- the main frame includes a first wall, a second wall which are arranged in sequence along the neutron beam direction and are circumferentially closed around the main axis, and a first horizontal plate connecting the first wall and the second wall,
- the first horizontal plate extends perpendicular to the direction of the neutron beam
- the first wall is used to install the transmission tube of the accelerator
- the second wall surrounds and forms the first containing unit
- the first wall The radial distance to the main shaft is smaller than the radial distance from the second wall to the main shaft.
- the basic part of the retarder surrounds the target, so that the neutrons generated by the target can be effectively retarded in all directions, which can further improve the neutron flux and beam quality.
- the main frame includes a third wall circumferentially closed around the neutron beam direction, and the radial distance from the second wall to the main axis is smaller than the radial distance from the third wall to the main axis
- the frame further includes first and second side plates respectively arranged on both sides of the third wall along the direction of the neutron beam and connected to the third wall, and the sub-frame includes A second horizontal plate arranged between the second wall and the second side plate.
- the sub-frame further includes a fourth wall which is circumferentially closed around the neutron beam direction and extends between the second transverse plate and the second side plate, and the neutron capture treatment system It also includes a collimator.
- the fourth wall forms the installation part and/or the beam exit of the collimator.
- the secondary frame made of carbon fiber is used in the beam exit direction. Compared with aluminum alloy, the activation degree is smaller. It has high strength and has a certain retarding effect.
- the sub-frame also serves as the installation part of the collimator.
- the main frame also includes a radial partition arranged between the first side plate and the second horizontal plate and extending from the first wall to the second wall or the third wall, the first wall , A second wall, a third wall, a first horizontal plate, a second horizontal plate and a first side plate surround the second accommodating unit, and the radial partition divides the second accommodating unit in the circumferential direction A number of sub-regions, the third wall, the fourth wall, the second horizontal plate and the second side plate surround to form a third accommodating unit.
- the second accommodating unit is also provided with at least the reflector/radiation shield In one part, at least part of the radiation shield is provided in the third accommodating unit, and the material of the first and second side plates is lead-antimony alloy. Lead can further shield the radiation. At the same time, the strength of the lead-antimony alloy is higher. high.
- the basic part is provided with a central hole on the first end surface facing the first side plate, and the central hole is used to accommodate the transmission tube and the target of the accelerator.
- the first end surface of the supplementary unit close to the second side plate is flush with the second end surface of the basic part close to the second side plate.
- a shielding plate is arranged adjacent to the second end surface of the basic part, the shielding plate is a lead plate, and the lead can absorb gamma rays released from the retarder, and the shielding plate is in the direction of the neutron beam.
- the stop member is arranged adjacent to the second horizontal plate, and the stop member is detachably connected to the main frame and/or the secondary frame to facilitate adjustment and replacement of the basic part of the retarder.
- a neutron capture treatment system including a neutron generating device and a beam shaping body, the neutrons generated by the neutron generating device form a neutron beam, and the neutron beam defines a main axis,
- the beam shaping body can adjust the beam quality of the neutron beam, the beam shaping body includes a retarder, a reflector and a radiation shielding body, and the retarder will be generated from the neutron generator
- the neutrons decelerate to the superthermal neutron energy zone
- the reflector surrounds the retarder and guides the neutrons that deviate from the main axis back to the main axis to increase the intensity of the superthermal neutron beam
- the radiation shield The body is used to shield the leaking neutrons and photons to reduce the normal tissue dose in the non-irradiated area.
- the beam shaping body also includes a frame for accommodating the retarder body.
- the frame includes a detachable main frame and a secondary frame. frame.
- the frame forms the positioning and support for the retarder, which can improve the flux and quality of the neutron radiation source; the main frame and the secondary frame can be detachably connected to facilitate the replacement of the retarder.
- the frame of the beam shaping body forms the positioning and support for the slow body, which can improve the flux and quality of the neutron radiation source.
- Figure 1 is a schematic diagram of the boron neutron capture reaction
- Figure 2 is the 10 B(n, ⁇ ) 7 Li neutron capture nuclear reaction equation
- Figure 3 is a schematic diagram of a neutron capture therapy system according to an embodiment of the present invention.
- FIG. 4 is a schematic diagram of a beam shaping body and a collimator of a neutron capture therapy system according to an embodiment of the present invention
- Fig. 5 is a schematic diagram of the frame in Fig. 4;
- Fig. 6 is a schematic diagram of the main frame in Fig. 5 viewed from the direction of the neutron beam N;
- Fig. 7 is a schematic diagram of the main frame in Fig. 5 viewed from the direction opposite to the direction of the neutron beam N.
- the neutron capture treatment system in this embodiment is preferably a boron neutron capture treatment system 100, which includes a neutron generator 10, a beam shaping body 20, a collimator 30 and a treatment table 40.
- the neutron generator 10 includes an accelerator 11 and a target T.
- the accelerator 11 accelerates charged particles (such as protons, deuterons, etc.) to produce a charged particle beam P such as a proton beam.
- the charged particle beam P irradiates the target T and interacts with
- the target material T acts to generate neutrons, the neutrons form a neutron beam N, the neutron beam defines a main axis X, and the target material T is preferably a metal target material.
- the direction of the neutron beam N in the figure and below does not represent the actual neutron movement direction, but the direction of the overall movement trend of the neutron beam N.
- Select the appropriate nuclear reaction according to the required neutron yield and energy, the available accelerated charged particle energy and current size, and the physical and chemical properties of the metal target.
- the nuclear reactions that are often discussed are 7 Li(p,n) 7 Be and 9 Be(p,n) 9 B, both of these reactions are endothermic reactions.
- the energy thresholds of the two nuclear reactions are 1.881 MeV and 2.055 MeV, respectively.
- the ideal neutron source for boron neutron capture therapy is superthermal neutrons with keV energy level, theoretically, if proton bombardment with an energy slightly higher than the threshold is used
- the metallic lithium target can generate relatively low-energy neutrons and can be used in clinics without too much slowing treatment.
- the two target materials of lithium metal (Li) and beryllium metal (Be) have proton interaction cross-sections with threshold energy Not high, in order to generate a large enough neutron flux, usually higher energy protons are used to initiate nuclear reactions.
- the ideal target material should have the characteristics of high neutron yield, neutron energy distribution close to the superthermal neutron energy region (described in detail below), no strong penetrating radiation, safe, cheap, easy to operate, and high temperature resistance.
- the target material T may also be made of metal materials other than Li and Be, for example, Ta or W and alloys thereof.
- the accelerator 11 may be a linear accelerator, a cyclotron, a synchrotron, or a synchrocyclotron.
- the neutron source of the boron neutron capture therapy produces a mixed radiation field, that is, the beam contains low to high energy neutrons and photons; for the boron neutron capture therapy of deep tumors, except for the superthermal neutrons, the rest of the radiation
- the human head tissue prosthesis is used for dose calculation, and the prosthetic beam quality factor is used as the neutron radiation
- the design reference of the bundle will be described in detail below.
- the International Atomic Energy Agency has given five recommendations for air beam quality factors for neutron sources for clinical boron neutron capture therapy. These five recommendations can be used to compare the pros and cons of different neutron sources and serve as Reference basis for selecting neutron generation methods and designing beam shaping bodies. The five recommendations are as follows:
- Thermal neutron to epithermal neutron flux ratio thermal to epithermal neutron flux ratio ⁇ 0.05
- the superthermal neutron energy range is between 0.5eV and 40keV, the thermal neutron energy range is less than 0.5eV, and the fast neutron energy range is greater than 40keV.
- the neutron beam flux and the concentration of boron-containing drugs in the tumor jointly determine the clinical treatment time. If the concentration of boron-containing drugs in the tumor is high enough, the requirement for neutron beam flux can be reduced; conversely, if the concentration of boron-containing drugs in the tumor is low, high flux superthermal neutrons are required to give the tumor a sufficient dose.
- the IAEA's requirement for the flux of the superthermal neutron beam is that the number of superthermal neutrons per square centimeter per second is greater than 10 9.
- the neutron beam under this flux can roughly control the treatment of current boron-containing drugs Within one hour, short treatment time not only has advantages in patient positioning and comfort, but also can effectively utilize the limited residence time of boron-containing drugs in tumors.
- fast neutrons can cause unnecessary normal tissue doses, they are regarded as pollution.
- the dose is positively correlated with neutron energy. Therefore, the content of fast neutrons should be minimized in the design of neutron beams.
- Fast neutron pollution is defined as the dose of fast neutrons per unit of superthermal neutron flux.
- the IAEA's recommendation for fast neutron pollution is less than 2x 10 -13 Gy-cm 2 /n.
- Gamma rays are strong penetrating radiation, which will non-selectively cause the dose deposition of all tissues in the beam path. Therefore, reducing the content of gamma rays is also a necessary requirement for neutron beam design.
- Gamma-ray pollution is defined as the unit superheated neutron flux accompanying The IAEA’s recommendation for ⁇ -ray pollution is less than 2x 10 -13 Gy-cm 2 /n.
- thermal neutrons Due to the fast attenuation speed and poor penetration ability of thermal neutrons, most of the energy is deposited in the skin tissue after entering the human body. Except for epidermal tumors such as melanoma, which need to use thermal neutrons as the neutron source for boron neutron capture therapy, it is targeted at the brain Deep tumors such as tumors should reduce thermal neutron content.
- the IAEA recommends that the ratio of thermal neutron to superthermal neutron flux is less than 0.05.
- the ratio of neutron current to flux represents the directionality of the beam. The larger the ratio, the better the forward direction of the neutron beam.
- the high forward neutron beam can reduce the normal tissue dose caused by neutron divergence. It also improves the treatment depth and the flexibility of the posture.
- the IAEA recommends that the ratio of neutron current to flux is greater than 0.7.
- the prosthesis is used to obtain the dose distribution in the tissue, and the beam quality factors of the prosthesis are derived according to the dose-depth curve of the normal tissue and the tumor.
- the following three parameters can be used to compare the therapeutic benefits of different neutron beams.
- the tumor dose is equal to the depth of the maximum dose of normal tissue. After this depth, the dose of tumor cells is less than the maximum dose of normal tissue, that is, the advantage of boron neutron capture is lost. This parameter represents the penetration ability of the neutron beam. The larger the effective treatment depth, the deeper the tumor can be treated, and the unit is cm.
- the effective treatment depth of tumor dose rate is also equal to the maximum dose rate of normal tissue. Because the total dose received by normal tissue is a factor that affects the total dose that can be given to the tumor, the parameter affects the length of the treatment time. The greater the effective treatment depth and the dose rate, the shorter the irradiation time required to give a certain dose to the tumor.
- the unit is cGy/mA -min.
- the effective treatment dose ratio received by the tumor and normal tissue is called the effective treatment dose ratio; the average dose can be calculated by integrating the dose-depth curve.
- RBE Relative Biological Effectiveness
- the neutron beam N generated by the neutron generator 10 is irradiated to the patient 200 on the treatment table 40 through the beam shaping body 20 and the collimator 30 in sequence.
- the beam shaping body 20 can adjust the beam quality of the neutron beam N generated by the neutron generator 10, and the collimator 30 is used to converge the neutron beam N so that the neutron beam N has a higher Targeting.
- the beam shaping body 20 further includes a frame 21 and a main body 23. At least part of the main body 23 is accommodated in the frame 21.
- the frame 21 supports the main body 23 to prevent deformation and damage of the material itself, which affects target replacement and beam quality.
- the main body 23 includes a retarder 231, a reflector 232, and a radiation shield 233.
- the neutrons generated by the neutron generator 10 have a wide energy spectrum. Except for the superthermal neutrons to meet the needs of treatment, it is necessary to reduce other types as much as possible. The neutron and photon content of the neutron to avoid harm to operators or patients.
- the body 231 is made of materials with a large interaction cross section with fast neutrons and a small interaction cross section with superthermal neutrons, such as D 2 O, Al, AlF 3 , MgF 2 , CaF 2 , LiF, Li 2 CO 3 or Al 2 O At least one of 3 ;
- the reflector 232 surrounds the retarder 231, and reflects the neutrons diffused through the retarder 231 back to the neutron beam N to improve the utilization of neutrons, and has the ability to reflect neutrons Made of strong materials, such as including at least one of Pb or Ni;
- the radiation shield 233 is used to shield the leaking neutrons and photons to reduce the normal tissue dose in the non-irradiated area, and the material of the radiation shield 233 includes photon shielding At least one of materials and neutron shielding materials, such as photon shielding material
- the main body can also have other structures, as long as the superthermal neutron beam required for treatment can be obtained.
- the target T is arranged between the accelerator 11 and the beam shaping body 20.
- the accelerator 11 has a transmission tube 111 for transmitting the charged particle line P.
- the transmission tube 111 extends along the direction of the charged particle line P and enters the beam shaping body 20.
- the target T is set in the retarder 231 and at the end of the transmission tube 111 to obtain a better neutron beam quality.
- the first and second cooling tubes D1 and D2 are arranged between the transmission tube 111 and the retarder 231 and the reflector 232.
- first and second cooling tubes D1 and D2 are respectively connected to the cooling target T
- the inlet (not shown) is connected to the cooling outlet (not shown), and the other end is connected to an external cooling source (not shown).
- first and second cooling pipes can also be arranged in the beam shaping body in other ways, and when the target is placed outside the beam shaping body, it can also be eliminated.
- the frame 21 includes a first wall 211 that is circumferentially closed around the main axis X, and a first wall 211 that is arranged on both sides of the first wall 211 along the neutron beam N direction and connected to the first wall 211.
- the side plates 221, 222, the first side plate 221 is provided with a hole 2211 through which the transmission tube 111 passes, the second side plate 222 is provided with a hole 2221 forming a beam exit, the first wall 211 and the first and second side plates 221
- a accommodating portion C of the retarder is formed between 222 and 222, and at least a part of the reflector and/or radiation shielding body is also arranged in the accommodating portion C.
- the accommodating part C includes at least one accommodating unit C1-C3 (detailed below), each accommodating unit C1-C3 accommodates at least one of the retarder 231, the reflector 232 and the radiation shielding body 233, and at least one accommodating unit simultaneously accommodates At least two of the retarder, the reflector and the radiation shielding body or contain at least two different materials at the same time.
- the retarder 231 includes a basic part and a supplementary part, and the basic part and the supplementary part are respectively accommodated in different accommodating units. It can be understood that the first and second side plates may not be provided, and the receiving part is surrounded by the first wall.
- the frame 21 also includes a first horizontal plate 223 arranged between the first and second side plates 221 and 222 along the neutron beam N direction, and is circumferentially closed around the main axis X and extends between the first horizontal plate 223 and the first side plate
- the second wall 212 between 221 and the third wall 213 circumferentially closed around the main axis X and extending from the first horizontal plate 223 to the second side plate 222.
- the second wall 212 is radially closer to the main axis X than the third wall 213.
- the third wall 213 is located between the first wall 211 and the second wall 212 in the radial direction.
- the first transverse plate 223 extends between the second wall 212 and the third wall 212. Between walls 213.
- the inner surface of the second wall 212 is on the same surface as the side wall of the hole 2211 on the first side plate 221, and the second wall 212 forms the installation part of the transmission pipe 111, the first and second cooling pipes D1, D2, etc. It can be understood that the first transverse plate may extend to the first wall.
- the frame 21 also includes a second horizontal plate 224 arranged between the third wall 213 and the second side plate 222 along the neutron beam N direction, which is circumferentially closed around the main axis X and extends on the second horizontal plate 224 and the second side plate
- the fourth wall 214 between 222 is adjacent to the third horizontal plate 225 arranged between the second horizontal plate 224 and the second side plate 222 adjacent to the second horizontal plate 224.
- the second horizontal plate 224 extends from the first wall 211 to the inner side of the third wall 213.
- the fourth wall 214 is located between the first wall 211 and the third wall 213 in the radial direction.
- the inner surface of the fourth wall 214 and the second side plate The side walls of the upper hole 2221 on the 222 are on the same surface.
- the fourth wall 214 and the hole 2221 on the second side plate 222 together form a beam exit.
- the third horizontal plate 225 forms a hole 2251 through which the neutron beam N passes.
- the third wall 213 is located radially between the fourth wall 214 and the inner wall of the hole 2251 on the third horizontal plate 225, and the outer wall of the third horizontal plate 225 is located between the inner surface of the fourth wall 214 and the inner surface of the third wall 213 .
- the cross-sections of the first, second, third, and fourth walls in the direction perpendicular to the main axis X are all rings around the main axis X and extend parallel to the main axis X, and the side plates and horizontal plates are all perpendicular to the main axis X.
- the flat plate extending from the main axis X can also have other settings, such as the extension direction is inclined to the main axis;
- the frame can also include multiple walls that are circumferentially closed around the main axis X and multiple horizontal plates arranged between the walls. Used to accommodate or support other parts of the beam shaping body.
- a columnar first housing unit C1 is formed in the direction of the neutron beam N.
- the first wall 211, the second wall 212, and the A second receiving unit C2 is formed between the three walls 213, the first side plate 221, the first horizontal plate 223, and the second horizontal plate 224, the first wall 211, the fourth wall 214, the second horizontal plate 224 and the second side plate
- a second containing unit C3 is formed between 222.
- the magnesium fluoride block 241 is provided in the first containing unit C1 as the basic part of the retarder 231.
- the magnesium fluoride block 241 contains Li-6 and can be used as a thermal neutron absorber at the same time.
- the magnesium fluoride block 241 is cylindrical as a whole.
- a central hole 2411 is provided facing the end surface of the first side plate 221.
- the central hole 2411 is used to accommodate the transfer pipe 111, the first and second cooling pipes D1, D2 and the target material T.
- the central hole 2411 is a cylindrical hole.
- the inner surface of the wall 2411a and the second wall 212 are on the same surface.
- the radial distance L1 from the second wall 212 to the main axis X is smaller than the radial distance L2 from the third wall 213 to the main axis X, so that the basic part of the retarder 231 surrounds
- the target material T enables the neutrons generated by the target material T to be effectively slowed down in all directions, which can further improve the neutron flux and beam quality.
- a lead plate 242 is arranged between the magnesium fluoride block 241 and the third horizontal plate 225. The lead plate 242 serves as a photon shield.
- the lead can absorb the gamma rays released from the retarder body, and the lead plate 242 is in the neutron beam N direction
- the thickness is less than or equal to 5cm, and the neutrons passing through the retarder will not be reflected. It is understood that other settings are also possible.
- the magnesium fluoride block 241 does not contain Li-6, but the magnesium fluoride block 241 and the second A separate thermal neutron absorber composed of Li-6 is arranged between the three horizontal plates 225, and the lead plate can also be eliminated.
- An aluminum alloy block 243 and a lead block 244 are arranged in the second accommodating unit C2.
- the aluminum alloy block 243 has surfaces in contact with the second wall 212, the third wall 213, and the first horizontal plate 223, so that the aluminum alloy block 243 serves as a retarder
- the supplementary part of 231 surrounds the basic part of the retarder 231 provided in the first accommodating unit C1.
- the aluminum alloy block 243 is used as a supplementary part of the retarder 231, which can reduce the manufacturing cost of the retarder, and at the same time, it will not greatly affect the beam quality.
- a PE block 245 of corresponding shape is provided in the third accommodating unit C3.
- the radiation shield 233 includes a neutron shield and a photon shield.
- the PE block 245 serves as the neutron shield
- the lead block 244 serves as both the reflector 232 and the photon shield. It can be understood that a PE block can also be provided in the second accommodating unit C2 as a neutron shield.
- Magnesium fluoride block 241 is made of slices, which is convenient for quality control and the beam intensity can be adjusted by increasing or decreasing the number of slices. As shown in the embodiment in Figure 4, when the magnesium fluoride block 241 is full, the magnesium fluoride block 241 and aluminum The end surface of the alloy block 243 close to the second side plate 222 is flush, and the lead plate 242 is arranged adjacent to the end surface of the magnesium fluoride block 241 close to the second side plate 222 and is in contact with the third horizontal plate 225. When the number of magnesium fluoride blocks 241 is reduced, a positioning ring 226 (as shown in FIG. 5) is provided between the lead plate 242 and the third horizontal plate 225 for corresponding supplementation.
- the positioning ring 226 can also be provided in the fluorine Between the magnesium block 241 and the lead plate 242, the third horizontal plate 225 serves as a stop ring, and the positioning ring 226 also has a hole 2261 for passing the neutron beam N with the same aperture as the stop ring.
- the positioning ring 226 of different thicknesses can be set in advance to play the role of positioning the magnesium fluoride block 241.
- the positioning ring 226 and the stop ring (third horizontal plate 225) are made of carbon fiber, which is a radioactive isotope generated after being activated by neutrons. The half-life is short. It can be understood that the positioning ring and the stop ring can also be replaced with other types of positioning and stop members.
- the positioning member can conveniently adjust the size of the retarder body, thereby adjusting the neutron beam flux, and the stop member can quickly and conveniently realize the packaging of the retarder body after adjustment.
- the PE as the neutron shield in this embodiment can be replaced with other neutron shielding materials; the lead as the photon shield can be replaced with other photon shielding materials; the lead as the reflector can be replaced with other neutron reflection capabilities Strong material; magnesium fluoride, which is the basic part of the retarder, can be replaced with other materials with a large fast neutron cross section and a small superthermal neutron cross section; Li-6 as a thermal neutron absorber can be replaced with other materials A material with a large cross-section with thermal neutrons; the aluminum alloy as a supplementary part of the retarder can be replaced with a material including at least one of Zn, Mg, Al, Pb, Ti, La, Zr, Bi, Si, and C, The supplementary part uses easily available materials, which can reduce the manufacturing cost of the retarder, and at the same time has a certain neutron retardation effect, which will not have a greater impact on the beam quality.
- the frame 21 is further provided with a radial partition 210.
- the plane on which the radial partition 210 is located extends through the main shaft X, and divides the second containing unit C2 into at least two sub-regions in the circumferential direction.
- the lead block and the aluminum alloy block arranged in the second containing unit C2 are equally divided into at least two sub-modules in the circumferential direction.
- the radial partition 210 is arranged between the first side plate 221 and the second horizontal plate 224, and extends from the first wall 211 to the second wall 212 or the third wall 213.
- the radial partition 210 is 4 There are a number of flat plates evenly distributed along the circumferential direction; it can be understood that there can be other numbers or arrangements, or no radial partitions.
- the radial partition 210, the first horizontal plate 223 and the first, second, and third walls 211-213 are integrated.
- the material is aluminum alloy, which has good mechanical properties and The radioisotope produced after being activated by neutrons has a short half-life.
- the casting process can be used, and the supporting mold is integrally formed.
- the template is wooden or aluminum mold, and the sand core can be red sand or resin sand.
- the specific process is a common method in the industry. Since casting will be accompanied by a draft angle, according to the design and beam quality requirements, machining needs to remove them all.
- the structure and casting process make the frame structure have the advantages of good integrity, high rigidity and high bearing capacity.
- the sub-frame 21b a carbon fiber composite material is used, and the specific process is a method commonly used in the industry.
- the radioisotopes produced by aluminum alloy and carbon fiber composite materials activated by neutrons have a short half-life and low radiation. Carbon fiber is used in the beam exit direction. Compared with aluminum alloy, the activation degree is smaller, and the strength is higher, and there is a certain retarding effect.
- the main frame 21a and the secondary frame 21b are connected by bolts.
- the first threaded hole is uniformly machined on the end surface of the third wall 213 facing the second side plate 222, and the position corresponding to the first threaded hole on the second horizontal plate 224 is evenly machined.
- the first through hole is machined, and the bolt passes through the first through hole to connect with the first threaded hole.
- a second threaded hole is uniformly reserved on the end surface of the third wall 213 facing the second side plate 222, and the second threaded hole is different from the first threaded hole.
- a second through hole is reserved at the position corresponding to the second threaded hole on the second horizontal plate 224, and the third through hole is machined on the stop ring (the third horizontal plate 225).
- the through holes correspond, the bolts pass through the third through holes, the second through holes and the second threaded holes in sequence, and the stop ring (third horizontal plate 225) is fixed to the main frame 21a by bolts. It can be understood that the stop ring is also Can be fixed to the subframe.
- a fourth through hole is machined on the stop ring (third horizontal plate 225). The position of the fourth through hole corresponds to the first through hole, and the hole diameter is slightly larger than the maximum of the head of the connecting bolt between the main frame 21a and the secondary frame 21b. The radial dimension is used to accommodate the bolt head. It is understood that the fourth through hole may also be a blind hole.
- the aperture of the first through hole is slightly larger than the aperture of the first threaded hole
- the aperture of the second and third through holes are slightly larger than the aperture of the second threaded hole
- the first threaded hole, the first through hole and the second threaded hole The number of the two threaded holes, the second through holes, and the third through holes may satisfy the connection strength. It is understandable that the secondary frame, positioning ring and stop ring may not be provided.
- the first and second side plates 221 and 222 are made of lead-antimony alloy materials. Lead can further shield radiation, and the lead-antimony alloy has higher strength.
- the first and second side plates 221, 222 and the main frame are connected by bolts, and the third threaded holes are uniformly machined on the inner wall of the main frame 21a facing the first and second side plates.
- the fourth through hole is uniformly machined at the position corresponding to the third threaded hole on the plates 221, 222. Considering the assembly of the bolt, the hole diameter of the fourth through hole is slightly larger than that of the third threaded hole. The number of through holes only needs to satisfy the connection strength.
- the materials of the main frame, sub-frame, side plate, positioning ring, and stop ring in this embodiment have a certain strength and the radioisotope produced by neutron activation has a short half-life (such as less than 7 days).
- the material performance can meet the support beam shaping body, such as aluminum alloy, titanium alloy, lead antimony alloy, cobalt-free steel, carbon fiber, PEEK, polymer, etc.; other connection methods can also be used, as long as the The detachable connection between the bit ring and the frame makes it easy to adjust and replace the basic part of the retarder; the secondary frame and the side plate and the main frame adopt a detachable connection or a non-detachable connection. When the detachable connection is adopted, it is easy to replace the main body. Parts.
- the frame and main body of the beam shaping body in this embodiment can also have other structures.
- the collimator 30 is arranged at the back of the beam exit, and the superthermal neutron beam from the collimator 30 irradiates the patient 200, and after passing through the shallow normal tissue, it is slowly turned into thermal neutrons to reach the tumor cell M.
- the collimator 30 and the sub-frame 21b are fixed by threaded connection, and the fourth wall 214 of the sub-frame 21b forms the mounting part of the collimator 30, and the collimator 30 is close to the beam shaping
- the end of the body 20 has a flange 31 surrounding the main shaft X.
- the outer wall of the flange 31 has an external thread (not shown), and the inner wall of the fourth wall 214 is provided with an internal thread (not shown) matching the external thread.
- the collimator 30 can also be fixed by other connection methods, and the collimator 30 can also be eliminated or replaced by other structures, and the neutron beam exits the beam exit to directly irradiate the patient 200.
- a radiation shielding device 50 is further provided between the patient 200 and the beam exit to shield the radiation from the beam exit to the normal tissue of the patient. It is understandable that the radiation shielding device 50 may not be provided.
- the "cylinder” or “cylinder-shaped” in the embodiment of the present invention refers to a structure whose overall trend of the outer contour is basically unchanged from one side to the other side of the direction shown in the figure.
- One of the outer contours The line can be a line segment, such as a corresponding contour line in a cylindrical shape, or a circular arc close to the line segment with a larger curvature, such as a corresponding contour line in a spherical shape with a larger curvature.
- the entire surface of the outer contour can be smooth Transitions can also be non-smooth transitions, for example, many protrusions and grooves are made on the surface of a cylinder or a spherical body with a larger curvature.
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Abstract
Description
Claims (15)
- 一种中子捕获治疗系统,包括中子产生装置和射束整形体,所述中子产生装置包括加速器和靶材,所述加速器加速产生的带电粒子线与所述靶材作用产生中子,所述中子形成中子束,所述中子束限定一根主轴,其特征在于,所述射束整形体包括缓速体、反射体和辐射屏蔽体,所述缓速体将自所述靶材产生的中子减速至超热中子能区,所述反射体包围所述缓速体并将偏离所述主轴的中子导回至所述主轴以提高超热中子束强度,所述辐射屏蔽体用于屏蔽渗漏的中子和光子以减少非照射区的正常组织剂量,所述射束整形体还包括容纳所述缓速体的框架。
- 根据权利要求1所述的中子捕获治疗系统,其特征在于,所述缓速体为可调整的,所述框架包括固定所述缓速体的定位构件和止位构件。
- 根据权利要求2所述的中子捕获治疗系统,其特征在于,所述定位构件和止位构件的材料被中子活化后产生的放射性同位素半衰期小于7天。
- 根据权利要求2所述的中子捕获治疗系统,其特征在于,所述定位构件和止位构件的材料为铝合金、钛合金、铅锑合金、不含钴的钢材、碳纤维、PEEK或高分子聚合物。
- 根据权利要求2所述的中子捕获治疗系统,其特征在于,所述缓速体包括基本部分和补充部分,所述基本部分和补充部分材料不同,所述框架形成至少一个容纳单元,所述容纳单元包括邻接的第一容纳单元和第二容纳单元,所述基本部分容纳在所述第一容纳单元内且为分片式可调整的,当减少所述基本部分的片数时,在所述第一容纳单元内设置所述定位构件进行补充,所述止位构件用于固定所述基本部分。
- 根据权利要求5所述的中子捕获治疗系统,其特征在于,所述框架包括可拆卸连接的主框架和次框架,所述第一容纳单元由所述主框架的至少一部分包围形成,所述第二容纳单元由所述主框架的至少一部分和所述次框架的至少一部分包围形成,所述补充部分容纳在所述第二容纳单元内。
- 根据权利要求6所述的中子捕获治疗系统,其特征在于,所述主框架的材料为铝合金,所述次框架的材料为碳纤维复合材料。
- 根据权利要求5所述的中子捕获治疗系统,其特征在于,所述基本部分的材料包括D 2O、Al、AlF 3、MgF 2、CaF 2、LiF、Li 2CO 3或Al 2O 3中的至少一种,所述基本部分含Li-6,所述基本部分同时作为所述热中子吸收体。
- 根据权利要求5所述的中子捕获治疗系统,其特征在于,所述补充部分的材料包括Zn、Mg、Al、Pb、Ti、La、Zr、Bi、C中的至少一种。
- 根据权利要求6所述的中子捕获治疗系统,其特征在于,所述主框架包括沿所述中子束方向依次设置并围绕所述主轴周向封闭的第一壁、第二壁及连接所述第一壁和第二壁的第一横板,所述第一横板垂直于所述中子束方向延伸,所述第一壁用于安装所述加速器的传输管,所述第二壁包围形成所述第一容纳单元,所述第一壁到所述主轴的径向距离小于所述第二壁到所述主轴的径向距离。
- 根据权利要求10所述的中子捕获治疗系统,其特征在于,所述主框架包括围绕所述中子束方向周向封闭的第三壁,所述第二壁到所述主轴的径向距离小于所述第三壁到所述主轴的径向距离,所述框架还包括沿所述中子束方向分别设置在所述第三壁两侧并与第三壁连接的第一、第二侧板,所述次框架包括沿所述中子束方向在所述第二壁和第二侧板之间设置的第二横板。
- 根据权利要求11所述的中子捕获治疗系统,其特征在于,所述次框架还包括围绕所述中子束方向周向封闭并延伸在所述第二横板和第二侧板之间的第四壁,所述中子捕获治疗系统还包括准直器,所述第四壁形成所述准直器的安装部和/或射束出口,所述主框架还包括设置在所述第一侧板和第二横板之间并从所述第一壁延伸到所述第二壁或第三壁的径向隔板,所述第一壁、第二壁、第三壁、第一横板、第二横板和第一侧板包围形成所述第二容纳单元,所述径向隔板将所述第二容纳单元在周向分为若干子区域,所述第三壁、第四壁、第二横板和第二侧板包围形成第三容纳单元,所述第二容纳单元内还设置有所述反射体/辐射屏蔽体的至少一部分,所述第三容纳单元内设置至少部分所述辐射屏蔽体,所述第一、第二侧板的材料为铅锑合金。
- 根据权利要求11所述的中子捕获治疗系统,其特征在于,所述基本部分在朝向所述第一侧板的第一端面设置中心孔,所述中心孔用于容纳所述加速器的传输管和靶材,当所述基本部分满装时,所述补充单元靠近所述第二侧板的第一端面与所述基本部分靠近所述第二侧板的第二端面平齐。
- 根据权利要求13所述的中子捕获治疗系统,其特征在于,与所述基本部分的第二端面邻接设置屏蔽板,所述屏蔽板为铅板,所述屏蔽板在所述中子束方向的厚度小于等于5cm,当减少所述基本部分的片数时,邻接所述屏蔽板 设置所述定位构件,所述止位构件邻接所述第二横板设置,所述止位构件可拆卸连接到所述主框架和/或次框架。
- 一种中子捕获治疗系统,包括中子产生装置和射束整形体,所述中子产生装置产生的中子形成中子束,所述中子束限定一根主轴,所述射束整形体能够调整所述中子束的射束品质,其特征在于,所述射束整形体包括缓速体、反射体和辐射屏蔽体,所述缓速体将自所述中子产生装置产生的中子减速至超热中子能区,所述反射体包围所述缓速体并将偏离所述主轴的中子导回至所述主轴以提高超热中子束强度,所述辐射屏蔽体用于屏蔽渗漏的中子和光子以减少非照射区的正常组织剂量,所述射束整形体还包括容纳所述缓速体的框架,所述框架包括可拆卸连接的主框架和次框架。
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108934120A (zh) * | 2017-05-26 | 2018-12-04 | 南京中硼联康医疗科技有限公司 | 用于中子线产生装置的靶材及中子捕获治疗系统 |
CN113750376A (zh) * | 2021-09-10 | 2021-12-07 | 中山大学 | 一种中子束束流整型靶站装置 |
CN114152635A (zh) * | 2021-10-15 | 2022-03-08 | 中国人民解放军军事科学院军事医学研究院 | 中子外照射后人体血管内中子能谱的等效模拟装置 |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN211188822U (zh) * | 2019-04-17 | 2020-08-07 | 中硼(厦门)医疗器械有限公司 | 中子捕获治疗系统及用于中子捕获治疗系统的射束整形体 |
CN111821580A (zh) * | 2019-04-17 | 2020-10-27 | 中硼(厦门)医疗器械有限公司 | 中子捕获治疗系统及用于中子捕获治疗系统的射束整形体 |
CN114522353A (zh) * | 2020-11-23 | 2022-05-24 | 南京中硼联康医疗科技有限公司 | 动物辐照系统及其辐照固定装置 |
JP2022150626A (ja) * | 2021-03-26 | 2022-10-07 | 住友重機械工業株式会社 | 治療準備装置、及び治療設備 |
CN115137993A (zh) * | 2021-03-31 | 2022-10-04 | 中硼(厦门)医疗器械有限公司 | 中子捕获治疗系统及其中子产生部回收方法 |
KR20240093753A (ko) * | 2021-10-27 | 2024-06-24 | 티에이이 라이프 사이언시스 엘엘씨 | 중성자 빔을 변환하기 위한 시스템, 디바이스 및 방법 |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006047115A (ja) * | 2004-08-04 | 2006-02-16 | Mitsubishi Heavy Ind Ltd | 中性子発生装置及びターゲット、並びに中性子照射システム |
CN104771837A (zh) * | 2015-04-03 | 2015-07-15 | 中国中原对外工程有限公司 | 一堆三照射座布局的抗癌核素中子刀 |
CN205334975U (zh) * | 2015-12-29 | 2016-06-22 | 上海核工程研究设计院 | 一种可更换式燃料贮存格架中子吸收材料组件 |
CN107802968A (zh) * | 2017-11-24 | 2018-03-16 | 北京新核医疗科技有限公司 | 减速过滤装置及中子放射治疗系统 |
CN108926784A (zh) * | 2017-05-26 | 2018-12-04 | 南京中硼联康医疗科技有限公司 | 中子捕获治疗系统及用于粒子线产生装置的靶材 |
CN208335758U (zh) * | 2018-06-20 | 2019-01-04 | 新奥科技发展有限公司 | 一种防护装置 |
Family Cites Families (42)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6319840Y2 (zh) * | 1979-03-06 | 1988-06-02 | ||
JP5429053B2 (ja) | 2010-05-31 | 2014-02-26 | ブラザー工業株式会社 | 現像剤供給装置 |
US20120330084A1 (en) * | 2011-06-27 | 2012-12-27 | Richard Harris Pantell | Neutron Source for Neutron Capture Therapy |
US9180313B2 (en) | 2012-02-22 | 2015-11-10 | Mitsubishi Electric Corporation | Range shifter and particle radiotherapy device |
JP6156970B2 (ja) * | 2012-12-06 | 2017-07-05 | 三菱重工メカトロシステムズ株式会社 | 中性子速度調整装置および中性子発生装置 |
TWI532056B (zh) * | 2013-10-15 | 2016-05-01 | 財團法人工業技術研究院 | 濾屏與中子束源 |
EP3133905B1 (en) * | 2014-12-08 | 2018-01-17 | Neuboron Medtech Ltd. | A beam shaping assembly for neutron capture therapy |
JP6843766B2 (ja) * | 2015-05-04 | 2021-03-17 | 南京中硼▲聯▼康医▲療▼科技有限公司Neuboron Medtech Ltd. | 中性子捕捉療法用ビーム整形アセンブリ |
NZ736841A (en) * | 2015-05-06 | 2022-07-29 | Neutron Therapeutics Inc | Neutron target for boron neutron capture therapy |
CN109011207B (zh) * | 2015-09-28 | 2020-10-16 | 南京中硼联康医疗科技有限公司 | 用于中子捕获治疗系统的射束诊断系统 |
WO2017054557A1 (zh) * | 2015-09-28 | 2017-04-06 | 南京中硼联康医疗科技有限公司 | 用于中子捕获治疗系统的射束诊断系统 |
US11740370B2 (en) * | 2015-09-28 | 2023-08-29 | Neuboron Medtech Ltd. | Radiation detection system and radiation detection method for neutron capture therapy system |
JP6722281B2 (ja) * | 2015-09-30 | 2020-07-15 | 南京中硼▲聯▼康医▲療▼科技有限公司Neuboron Medtech Ltd. | 中性子捕捉療法に用いられるビーム整形体 |
CN109771845B (zh) * | 2015-10-15 | 2021-07-16 | 南京中硼联康医疗科技有限公司 | 中子缓速材料 |
RU2717364C1 (ru) * | 2015-11-12 | 2020-03-23 | Нойборон Медтех Лтд. | Система нейтрон-захватной терапии |
EP3369457B1 (en) * | 2015-11-26 | 2019-11-27 | Neuboron Medtech Ltd. | Beam shaping body for neutron capture therapy |
CN106798969B (zh) * | 2015-11-26 | 2023-05-16 | 南京中硼联康医疗科技有限公司 | 用于中子捕获治疗的射束整形体 |
WO2017118291A1 (zh) * | 2016-01-08 | 2017-07-13 | 南京中硼联康医疗科技有限公司 | 用于中子捕获治疗的射束整形体 |
EP3632509B1 (en) * | 2016-01-15 | 2022-08-31 | Neuboron Medtech Ltd. | Neutron capture therapy system |
JP6732244B2 (ja) * | 2016-03-25 | 2020-07-29 | 株式会社八神製作所 | 中性子減速照射装置 |
WO2018006550A1 (zh) * | 2016-07-04 | 2018-01-11 | 南京中硼联康医疗科技有限公司 | 中子治疗装置 |
WO2018006551A1 (zh) * | 2016-07-04 | 2018-01-11 | 南京中硼联康医疗科技有限公司 | 中子治疗装置 |
JP6782359B2 (ja) * | 2016-10-28 | 2020-11-11 | 南京中硼▲聯▼康医▲療▼科技有限公司Neuboron Medtech Ltd. | 中性子捕捉治療のためのビーム成形体 |
EP3517172B1 (en) * | 2016-10-31 | 2021-04-14 | Neuboron Medtech Ltd. | Neutron capture therapy system |
RU2721658C1 (ru) * | 2016-11-14 | 2020-05-21 | Нойборон Медтех Лтд. | Устройство и способ экранирования излучения на основе медицинских изображений |
EP3777976A1 (en) * | 2016-12-23 | 2021-02-17 | Neuboron Medtech Ltd. | Neutron capture therapy system and target for particle beam generating device |
JP6935878B2 (ja) * | 2017-03-27 | 2021-09-15 | 株式会社八神製作所 | 中性子減速照射装置及び延長コリメータ |
EP3527261B1 (en) * | 2017-03-29 | 2021-06-16 | Neuboron Medtech Ltd. | Radiation irradiation system and positioning component for radiation irradiation system |
WO2018205403A1 (zh) * | 2017-05-12 | 2018-11-15 | 南京中硼联康医疗科技有限公司 | 光子发射检测装置及具有其的硼中子捕获治疗系统 |
RU2734955C1 (ru) * | 2017-06-05 | 2020-10-26 | Нойборон Медтех Лтд. | Блок формирования пучка для нейтронно-захватной терапии |
US10462893B2 (en) * | 2017-06-05 | 2019-10-29 | Neutron Therapeutics, Inc. | Method and system for surface modification of substrate for ion beam target |
CN117130035A (zh) * | 2017-08-18 | 2023-11-28 | 南京中硼联康医疗科技有限公司 | 生物剂量计及具有其的中子捕获治疗系统 |
CN111494812B (zh) * | 2017-08-18 | 2022-03-22 | 南京中硼联康医疗科技有限公司 | 用于慢化中子的缓速体 |
RU2743972C1 (ru) * | 2017-08-24 | 2021-03-01 | Нойборон Медтех Лтд. | Система нейтрон-захватной терапии |
TWI687249B (zh) * | 2017-08-30 | 2020-03-11 | 中國商南京中硼聯康醫療科技有限公司 | 中子捕獲治療系統 |
WO2019047697A1 (zh) * | 2017-09-07 | 2019-03-14 | 南京中硼联康医疗科技有限公司 | 中子捕获治疗系统 |
WO2019114307A1 (zh) * | 2017-12-15 | 2019-06-20 | 南京中硼联康医疗科技有限公司 | 中子捕获治疗系统 |
RU2739171C1 (ru) * | 2017-12-15 | 2020-12-21 | Нойборон Медтех Лтд. | Система нейтронозахватной терапии |
CN208372315U (zh) * | 2017-12-15 | 2019-01-15 | 南京中硼联康医疗科技有限公司 | 中子捕获治疗系统 |
CN111714786A (zh) * | 2019-03-18 | 2020-09-29 | 中硼(厦门)医疗器械有限公司 | 中子捕获治疗系统 |
CN210728446U (zh) * | 2019-04-17 | 2020-06-12 | 中硼(厦门)医疗器械有限公司 | 中子捕获治疗系统 |
CN111821580A (zh) * | 2019-04-17 | 2020-10-27 | 中硼(厦门)医疗器械有限公司 | 中子捕获治疗系统及用于中子捕获治疗系统的射束整形体 |
-
2019
- 2019-04-17 CN CN201910308038.8A patent/CN111821580A/zh active Pending
-
2020
- 2020-03-17 EP EP20791847.5A patent/EP3957363A4/en active Pending
- 2020-03-17 CA CA3135519A patent/CA3135519A1/en active Pending
- 2020-03-17 WO PCT/CN2020/079731 patent/WO2020211583A1/zh unknown
- 2020-03-17 AU AU2020258593A patent/AU2020258593B2/en active Active
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-
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- 2021-10-06 US US17/494,876 patent/US12023524B2/en active Active
-
2024
- 2024-02-16 JP JP2024021734A patent/JP2024050931A/ja active Pending
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006047115A (ja) * | 2004-08-04 | 2006-02-16 | Mitsubishi Heavy Ind Ltd | 中性子発生装置及びターゲット、並びに中性子照射システム |
CN104771837A (zh) * | 2015-04-03 | 2015-07-15 | 中国中原对外工程有限公司 | 一堆三照射座布局的抗癌核素中子刀 |
CN205334975U (zh) * | 2015-12-29 | 2016-06-22 | 上海核工程研究设计院 | 一种可更换式燃料贮存格架中子吸收材料组件 |
CN108926784A (zh) * | 2017-05-26 | 2018-12-04 | 南京中硼联康医疗科技有限公司 | 中子捕获治疗系统及用于粒子线产生装置的靶材 |
CN107802968A (zh) * | 2017-11-24 | 2018-03-16 | 北京新核医疗科技有限公司 | 减速过滤装置及中子放射治疗系统 |
CN208335758U (zh) * | 2018-06-20 | 2019-01-04 | 新奥科技发展有限公司 | 一种防护装置 |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108934120A (zh) * | 2017-05-26 | 2018-12-04 | 南京中硼联康医疗科技有限公司 | 用于中子线产生装置的靶材及中子捕获治疗系统 |
CN108934120B (zh) * | 2017-05-26 | 2024-04-12 | 南京中硼联康医疗科技有限公司 | 用于中子线产生装置的靶材及中子捕获治疗系统 |
CN113750376A (zh) * | 2021-09-10 | 2021-12-07 | 中山大学 | 一种中子束束流整型靶站装置 |
CN114152635A (zh) * | 2021-10-15 | 2022-03-08 | 中国人民解放军军事科学院军事医学研究院 | 中子外照射后人体血管内中子能谱的等效模拟装置 |
CN114152635B (zh) * | 2021-10-15 | 2024-05-31 | 中国人民解放军军事科学院军事医学研究院 | 中子外照射后人体血管内中子能谱的等效模拟装置 |
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