WO2024099252A1 - 硼中子捕获治疗系统及其治疗计划生成方法 - Google Patents

硼中子捕获治疗系统及其治疗计划生成方法 Download PDF

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WO2024099252A1
WO2024099252A1 PCT/CN2023/129862 CN2023129862W WO2024099252A1 WO 2024099252 A1 WO2024099252 A1 WO 2024099252A1 CN 2023129862 W CN2023129862 W CN 2023129862W WO 2024099252 A1 WO2024099252 A1 WO 2024099252A1
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region
concentration
interest
drug
boron
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PCT/CN2023/129862
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French (fr)
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刘渊豪
邓逸樵
陈江
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中硼(厦门)医疗器械有限公司
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  • the present application relates to the technical field of radiotherapy, and in particular to a boron neutron capture therapy system and a method for generating a treatment plan thereof.
  • radiotherapy has become one of the main means 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 is often not effective for the treatment of malignant tumors that are more resistant to radiation (such as glioblastoma multiforme and melanoma).
  • boron neutron capture therapy in neutron capture therapy provides a better cancer treatment option than traditional radiotherapy by specifically aggregating boron-containing drugs in tumor cells and coordinating precise neutron beam control.
  • BNCT Boron Neutron Capture Therapy
  • 10B Boron Neutron Capture Therapy
  • 10B boron
  • 10B neutron
  • n, ⁇ 7Li neutron capture and nuclear fission reaction
  • two heavily charged particles 4He and 7Li
  • the average energy of the two heavily charged particles is about 2.33MeV, with high linear energy transfer (LET) and short range characteristics.
  • the linear energy transfer and range of ⁇ particles are 150keV/ ⁇ m and 8 ⁇ m, respectively, while those of 7Li heavy charged particles are 175keV/ ⁇ m and 5 ⁇ m.
  • the total range of the two particles is approximately equivalent to the size of a cell. Therefore, the radiation damage caused to the organism can be limited to the cellular level.
  • boron-containing drugs selectively accumulate in tumor cells and are combined with appropriate neutron sources, the purpose of locally killing tumor cells can be achieved without causing too much damage to normal tissues.
  • the three-dimensional model can simulate the absorbed dose of the human body under certain radiation conditions to help doctors formulate treatment plans. It is often necessary to use computer technology to perform various processing on medical imaging data to establish an accurate lattice model required by the Monte Carlo software, and combine it with the Monte Carlo software for simulation calculations.
  • the boron concentration information is based on The boron concentration data of the sample is obtained by blood sample test or biopsy, and the corresponding tissue and tumor boron concentration is inferred from it, so as to give the regional boron concentration value in the corresponding model area.
  • the given boron concentration information does not take into account the actual distribution of boron drugs in the organism and the metabolism of boron drugs over time, which in turn affects the reliability of the dose calculation results, resulting in low accuracy of the treatment plan and failure to achieve satisfactory treatment effects.
  • the present invention provides a boron neutron capture therapy system, which includes: a neutron beam irradiation device for generating a neutron beam and irradiating an irradiated body; a treatment planning module for assigning a boron concentration to each voxel unit in a three-dimensional voxel prosthesis tissue model and generating a treatment plan; and a control module for controlling the neutron beam irradiation device to perform irradiation according to the treatment plan.
  • the treatment planning module groups the regions of interest in the three-dimensional voxel prosthetic tissue model based on the standard uptake values and calculates an average value of the standard uptake values of each group.
  • I is the number of groups, which is set to an even number in one embodiment of the present invention
  • SUV ROI,upper is the upper limit of the SUV value in the region of interest
  • SUV ROI,lower is the lower limit of the SUV value in the region of interest.
  • group number I is greater than or equal to 10 and less than or equal to 500.
  • group number I is greater than or equal to 10 and less than or equal to 100.
  • group number I is equal to 40, 44, 50, 54 or 60.
  • the treatment planning module adjusts the number of groups I or the average SUV value based on a normalization factor k, and the normalization factor k is calculated using Formula 3:
  • SUV ROI (V) is the SUV value of the Vth voxel in the region of interest
  • ⁇ V SUV ROI (V)dV is the total SUV value before grouping
  • Ni is the count of the i-th group
  • k is the normalization factor
  • It is the total value of SUV after grouping.
  • N B10 ,group(V), Formula 4 is as follows:
  • ⁇ is a constant conversion factor used to convert the SUV value to the corresponding number of 10 B atoms
  • i represents the group index
  • SUV ROI (V) is the SUV value of the Vth voxel in the region of interest.
  • a second aspect of the present invention provides a boron neutron capture therapy system, comprising a neutron irradiation device for generating a neutron beam and irradiating an irradiated body; a treatment planning module for determining at least a high-concentration drug absorption region and a low-concentration drug absorption region based on a region of interest of the irradiated body, assigning drug concentrations and performing dose evaluation on the high-concentration drug absorption region and the low-concentration drug absorption region, and generating a treatment plan; and a control module for controlling the neutron irradiation device to execute the treatment plan.
  • the treatment plan module includes:
  • a modeling module used for establishing a three-dimensional voxel tissue model based on the medical imaging data of the irradiated body
  • a processing module configured to define a region of interest based on the three-dimensional voxel tissue model, determine at least a high-concentration drug absorption region and a low-concentration drug absorption region based on the region of interest, and group the high-concentration drug absorption region and the low-concentration drug absorption region, wherein the high-concentration drug absorption region is divided into at least one group, and the low-concentration drug absorption region is divided into at least two groups, and drug concentration is assigned to each group;
  • a dose assessment module which performs dose assessment based on the drug concentration and the irradiation parameters of the neutron beam
  • a treatment plan generating module generates a treatment plan based on the result of the dose evaluation.
  • the treatment planning module is further used to define TBR as the ratio of the drug concentration in the region of interest to the drug concentration in the blood, and define TNR as the ratio of the drug concentration in the region of interest to the drug concentration in normal tissue;
  • the processing module is used to determine that the area where the TBR of the region of interest is greater than or equal to the first specified value or the area where the TNR is greater than or equal to the second specified value is the high concentration drug absorption area, and determine that the area where the TBR of the region of interest is less than the first specified value or the area where the TNR is less than the second specified value is the low concentration drug absorption area.
  • the drug is a boron drug.
  • concentration of boron drug taken up by normal tissue is lower than the boron concentration in blood, that is, the TNR for the same region of interest is greater than the TBR, the first designated value is greater than or equal to 1.2, and the second designated value is greater than or equal to 1.5.
  • the drug is BPA
  • the uptake of BPA by the human body is that the boron concentration of normal tissue is similar to the boron concentration of blood, that is, for the same region of interest, TNR is equal to TBR, the first designated value is equal to 2.5, and the second designated value is equal to 2.5.
  • the drug is 18 F-BPA labeled with radioactive nuclides.
  • the processing module is used to divide the regions of interest into three groups, wherein the high concentration drug The absorption area is divided into one group, which is the first zone; the low-concentration drug absorption area is divided into two groups, which are the second zone and the third zone, wherein the area where the TBR of the low-concentration drug absorption area is greater than or equal to the third specified value or the TNR is greater than or equal to the fourth specified value is the second zone, and the area where the TBR of the low-concentration drug absorption area is less than the third specified value or the TNR is less than the fourth specified value is the third zone, the third specified value is greater than 1.5 and less than or equal to 2.0, and the fourth specified value is equal to the third specified value.
  • the third specified value is equal to the fourth specified value, which is equal to 2.0.
  • the drug is a radionuclide labeled drug
  • the treatment planning system is also used to convert the drug concentration into a numerical value among the radioactivity of the marker, the radioactivity intensity of the marker, the number of atoms decaying per unit time, the effective count of mutual destructive photons, and the standard uptake value obtained based on medical imaging data for quantitative or semi-quantitative analysis.
  • the drug is a boron drug labeled with a radionuclide
  • the treatment planning system is used to convert the drug concentration into a standard uptake value SUV for quantitative analysis.
  • N B10 (V) represents the number of 10 B atoms in the Vth region
  • ⁇ is a constant conversion factor
  • the third aspect of the present invention provides a method for generating a treatment plan for a boron neutron capture therapy system, which includes the following steps: establishing a three-dimensional voxel prosthetic tissue model with tissue type and tissue density data; assigning a boron concentration to each voxel unit in the three-dimensional voxel prosthetic tissue model; obtaining a dose distribution; and generating a treatment plan by optimizing the irradiation angle based on the calculation results.
  • the step of establishing a three-dimensional voxel prosthetic tissue model with tissue type and tissue density data includes: reading medical image data; establishing a three-dimensional medical image voxel model; defining the boundaries of the region of interest; and defining the tissue type (element composition) and tissue density of each voxel unit.
  • the step of assigning a boron concentration value to each voxel unit in the three-dimensional voxel prosthetic tissue model includes: grouping the regions of interest based on standard uptake values; and determining the boron concentration in each voxel in the region of interest.
  • the step of grouping the regions of interest includes the step of converting the 10 B information in each voxel in the region of interest in the image into an SUV value by using Formula 1, and Formula 1 is as follows:
  • ROI is the region of interest defined in the image
  • Acitivity Concentration in ROI is the average radioactivity per unit volume in the region of interest
  • Injected Dose is the injected radioactivity
  • body weight is the weight of the irradiated body.
  • the step of grouping the regions of interest is as follows: adjusting the number of groups I or SUV by the normalization factor k average value.
  • SUV ROI (V) is the SUV value of the Vth voxel in the region of interest
  • ⁇ V SUV ROI (V)dV is the total SUV value before grouping
  • Ni is the count of the i-th group
  • k is the normalization factor
  • ⁇ is a constant conversion factor used to convert the SUV value to the corresponding number of 10 B atoms
  • i represents the group index
  • SUV ROI (V) is the SUV value of the Vth voxel in the region of interest.
  • the fourth aspect of the present invention provides a method for generating a treatment plan for a boron neutron capture therapy system, comprising: establishing a three-dimensional voxel tissue model based on medical imaging data of an irradiated body; defining a region of interest based on the three-dimensional voxel tissue model; determining at least a high-concentration drug absorption region and a low-concentration drug absorption region based on the region of interest, and grouping the high-concentration drug absorption region and the low-concentration drug absorption region, wherein the high-concentration drug absorption region is divided into at least one group, and the low-concentration drug absorption region is divided into at least two groups, and drug concentration is assigned to each group; performing dose evaluation based on the drug concentration and irradiation parameters of the neutron beam to obtain dose distribution; and generating a treatment plan by optimizing the irradiation angle according to the calculation results.
  • the step of determining at least a high-concentration drug absorption region and a low-concentration drug absorption region based on the region of interest includes: defining TBR as the ratio of the drug concentration in the region of interest to the drug concentration in the blood, defining TNR as the ratio of the drug concentration in the region of interest to the drug concentration in normal tissue; determining a region in which the TBR of the region of interest is greater than or equal to a first specified value or a region in which the TNR is greater than or equal to a second specified value as the high-concentration drug absorption region, and determining a region in which the TBR of the region of interest is less than the first specified value or a region in which the TNR is less than the second specified value as the Describe the low concentration drug absorption area.
  • the drug is a boron drug
  • the first designated value is greater than or equal to 1.2
  • the second designated value is greater than or equal to 1.5.
  • the drug is BPA
  • the first designated value is equal to the second designated value, which is 2.5.
  • the drug is 18 F-BPA labeled with radioactive nuclides.
  • the regions of interest are divided into three groups, wherein the high-concentration drug absorption region is divided into one group, namely the first zone; the low-concentration drug absorption region is divided into two groups, namely the second zone and the third zone, the region where the TBR of the low-concentration drug absorption region is greater than or equal to the third specified value or the TNR is greater than or equal to the fourth specified value is the second zone, the region where the TBR of the low-concentration drug absorption region is less than the third specified value or the TNR is less than the fourth specified value is the third zone, the third specified value is equal to the fourth specified value, and the third specified value is greater than 1.5 and less than or equal to 2.0.
  • the third specified value is equal to the fourth specified value, which is equal to 2.0.
  • the drug is a boron drug labeled with a radionuclide, and the drug concentration is converted into a standard uptake value SUV for quantitative analysis.
  • N B10 (V) represents the number of 10 B atoms in the Vth region
  • ⁇ is a constant conversion factor
  • the step of defining the region of interest includes: acquiring first image data of the irradiated object; acquiring second image data of the irradiated object; aligning the first image data with the second image data to obtain fused image data; and delineating the region of interest based on the fused image data.
  • the first image data is CT or MRI
  • the second image data is radionuclide medical image data.
  • the treatment planning module of the boron neutron capture therapy system provided in the first and third aspects of the present invention assigns corresponding boron concentration data to each voxel unit, and then combines the medical imaging data to perform dose simulation to formulate a treatment plan, so that the distribution of boron atoms in the region of interest is more in line with the actual situation, which can improve the accuracy of model establishment and dose calculation, ensure the accuracy of the treatment plan, and thus ensure the treatment effect.
  • the boron neutron capture therapy system and dose assessment method provided in the second and fourth aspects of the present invention divide the region of interest into at least a high-concentration drug absorption region and a low-concentration drug absorption region, avoiding the problem of a large number of boron concentration values increasing the Monte Carlo simulation calculation time when there are too many groupings, and also avoiding the problem of insufficient calculation reliability caused by a single boron concentration assignment; at the same time, by improving the accuracy and reliability of dose assessment, the treatment plan is further optimized.
  • This application can not only ensure the accuracy of dose calculation and ensure that the lesion range obtains a sufficient prescribed dose, but also significantly reduce the Monte Carlo simulation calculation time. It can reduce the amount of data and shorten the calculation time, so that treatment plans can be generated more quickly and accurately, and the operating efficiency of the treatment system can be improved.
  • FIG1 is a schematic diagram of a boron neutron capture reaction.
  • FIG. 2 is the 10 B(n, ⁇ ) 7 Li neutron capture nuclear reaction equation.
  • FIG. 3 is a block diagram of a neutron capture therapy system according to an embodiment of the present invention.
  • FIG. 4 is a schematic structural diagram of a neutron irradiation device in an embodiment of the present invention.
  • FIG. 5 is a flow chart of a method for generating a treatment plan according to an embodiment of the present invention.
  • FIG. 6 is a flow chart of a method for establishing a three-dimensional voxel prosthetic tissue model according to an embodiment of the present invention.
  • FIG. 7 is a flow chart of a method for determining boron concentration data for each voxel unit in a given three-dimensional voxel prosthetic tissue model according to an embodiment of the present invention.
  • FIG8 is a schematic flow chart of a method for evaluating a dose of boron neutron capture therapy in another embodiment of the present invention.
  • FIG. 9 is a schematic diagram of a CTsim image and a lesion area in another embodiment of the present invention.
  • FIG. 10 is a schematic diagram of a fused image and a region of interest in another embodiment of the present invention.
  • FIG. 11 is a schematic diagram of partitioning of a region of interest in another embodiment of the present invention.
  • FIG. 12 is a TBR-volume histogram of a region of interest in another embodiment of the present invention.
  • FIG. 13 is a comparison diagram of the dose-volume histogram of another embodiment of the present invention and the control group.
  • Boron neutron capture therapy system 100 neutron beam irradiation device 10, neutron generating device 11, treatment table 12, image acquisition module 20, treatment planning module 30, control module 40; neutron irradiation device 100, radiation generating device 110, accelerator 111, beam transmission device 112, beam shaper 120, collimator 126, reflector 121, retarder 122, thermal neutron absorber 123, radiation shielding body 124, beam channel 125.
  • a neutron capture therapy system and a method for generating a treatment plan thereof are taken as embodiments of the present invention.
  • Neutron capture therapy especially boron neutron capture therapy, will be briefly introduced below.
  • BNCT Boron Neutron Capture Therapy
  • 10B boron
  • 10B boron
  • the average energy of the two charged particles is about 2.33MeV, with high linear transfer and short range characteristics, and the alpha particle
  • the linear energy transfer amount and range are 150keV/ ⁇ m and 8 ⁇ m respectively, while the 7Li heavy-load particle is 175keV/ ⁇ m and 5 ⁇ m.
  • the total range of the two particles is approximately equivalent to the size of a cell. Therefore, the radiation damage caused to the organism can be limited to the cellular level.
  • boron-containing drugs selectively accumulate in tumor cells and are combined with appropriate neutron radiation sources, the purpose of locally killing tumor cells can be achieved without causing too much damage to normal tissues.
  • the Monte Carlo method can accurately simulate the collision trajectory and energy distribution of nuclear particles in the three-dimensional space inside the irradiated target.
  • boron neutron capture therapy in order to simulate the absorbed dose of the human body under certain radiation conditions to help doctors formulate treatment plans, it is often necessary to use computer technology to perform various processing on medical images to establish an accurate lattice model required by the Monte Carlo software, and combine the Monte Carlo software to perform simulation calculations to finally obtain the treatment plan.
  • the medical imaging data can be magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), PET-CT or X-ray imaging. However, it is well known to those skilled in the art that other medical imaging data can also be used. As long as the medical imaging data can be converted into a three-dimensional voxel prosthetic tissue model, it can be applied to the radiotherapy system and treatment plan generation method disclosed in the present invention.
  • a boron neutron capture therapy system 100 includes a neutron beam irradiation device 10, an image acquisition module 20, a treatment plan module 30, and a control module 40.
  • the neutron beam irradiation device 10 includes a neutron generator 11 and a treatment table 12.
  • the neutron generator 11 is used to generate a therapeutic neutron beam N during irradiation therapy and irradiate the irradiated body on the treatment table 12 that has taken in a boron ( 10 B) drug for treatment.
  • the treatment plan module 30 Before treatment, the treatment plan module 30 generates a treatment plan based on the medical image data of the irradiated part of the irradiated body and the parameters of the therapeutic neutron beam N generated by the neutron generator 11.
  • the control module 40 retrieves the treatment plan corresponding to the current irradiated body from the treatment plan module 30, and controls the neutron beam irradiation device 10 to perform irradiation according to the treatment plan.
  • the parameters of the therapeutic neutron beam N used by the treatment plan module 30 to generate the treatment plan are neutron beam models generated based on radiation source parameters.
  • the neutron irradiation device 100 includes a radiation generating device 110 and a beam shaping body 120.
  • the radiation generating device 110 includes an accelerator 111, a beam transmission device 112 and a target T.
  • the accelerator 111 accelerates charged particles (such as protons, deuterons, etc.) to generate charged particle lines P such as proton lines.
  • the charged particle lines P irradiate the target T and react with the target T to generate neutron lines (neutron beams) N.
  • the target T is preferably a metal target material. In the embodiment of the present invention, a target material made of lithium metal is preferably used.
  • the material of the target can also be made of metal materials other than lithium and beryllium, such as tantalum (Ta) or tungsten (W); the target can be in the shape of a disk, or in other solid shapes, or a liquid (liquid metal) can be used.
  • metal materials other than lithium and beryllium, such as tantalum (Ta) or tungsten (W); the target can be in the shape of a disk, or in other solid shapes, or a liquid (liquid metal) can be used.
  • the end of the beam shaper 120 close to the irradiated body M has a collimator 126 for converging the neutron beam.
  • the beam shaper 120 adjusts the beam quality of the neutron beam.
  • the neutron beam N generated by the radiation generating device 20 passes through the neutron beam of the beam shaper 120 in turn and irradiates the irradiated body M from the beam outlet 127.
  • the collimator 126 is used to converge the neutron beam so that the neutron beam is It is understood that the present embodiment may not have the collimator 126, and the beam directly irradiates the irradiated object M after coming out of the beam shaping body 120.
  • the beam shaping body 120 further includes a reflector 121, a retarder 122, a thermal neutron absorber 123, a radiation shield 124 and a beam channel 125. Since the neutrons generated by the radiation generating device 110 have a wide energy spectrum, in addition to epithermal neutrons that meet the treatment needs, it is necessary to reduce the content of other types of neutrons and photons as much as possible to avoid causing harm to the operator or the irradiated object. Therefore, the neutrons from the target T need to pass through the retarder 2212 to adjust the fast neutron energy (>10keV) to the epithermal neutron energy zone (0.5eV-10keV) and reduce the thermal neutron ( ⁇ 0.5eV) as much as possible.
  • the retarder 2212 is made of a material with a large cross section for fast neutrons and a small cross section for epithermal neutrons, preferably D2O , AlF3 , FluentalTM , CaF2 , Li2CO3 , MgF2 and Al2O .
  • the reflector 121 surrounds the retarder 122, and reflects the neutrons that diffuse through the retarder 122 to the surroundings back to the neutron beam N to improve the utilization rate of the neutrons, and is made of a material with strong neutron reflection ability, preferably at least one of Pb or Ni;
  • the retarder 122 has a thermal neutron absorber 123 at the rear, which is made of a material with a large cross-section for interacting with thermal neutrons, preferably Li-6, and is used to absorb thermal neutrons that pass through the retarder 122 to reduce the content of thermal neutrons in the neutron beam N, and avoid excessive doses to shallow normal tissues during treatment.
  • the thermal neutron absorber 123 can also be integrated with the retarder, and the material of the retarder contains Li-6; the radiation shielding body 124 is used to shield neutrons and photons that leak from the part outside the beam channel 125.
  • the material of the radiation shielding body 124 includes at least one of a photon shielding material and a neutron shielding material.
  • the material of the radiation shielding body 124 includes a photon shielding material lead (Pb) and a neutron shielding material polyethylene (PE).
  • the beam outlet 127 is disposed at the rear of the beam channel 125.
  • the epithermal neutron beam exiting the beam outlet 127 irradiates the irradiated body, and is slowed down to thermal neutrons after passing through the shallow normal tissue and reaches the tumor cells of the irradiated body M.
  • the control module 20 retrieves the treatment plan corresponding to the current patient from the treatment planning system 10, and controls the irradiation of the neutron irradiation device 100 according to the treatment plan.
  • the irradiated body needs to take radioactively labeled boron ( 10B )-containing drugs before treatment and obtain boron ( 10B ) concentration related information through radionuclide medical imaging (such as PET), that is, the medical imaging data of the irradiated part of the irradiated body includes tissue related information and boron concentration related information.
  • radionuclide medical imaging scanning equipment uses the positrons generated by the decay of radionuclides to meet the electrons in the tissue to produce positron-electron annihilation reaction.
  • the photomultiplier tube (PMT) and other detectors can detect the gamma rays emitted by the annihilation reaction.
  • the computer forms a cross-sectional image reflecting the distribution of positron radioisotopes, thereby obtaining boron concentration related information.
  • 18F -BPA-PET is used as a marker for scanning, and the raw data of each lattice of the image is converted into the image lattice intensity of each lattice of the PET image as the output of medical imaging data, and 18F is marked on BPA, so the raw data on the PET image can be used as the basis for 10B quantification.
  • the raw data on the images can also be used as the basis for 10 B quantification.
  • the Standard Uptake Value is a semi-quantitative indicator for radionuclide medical imaging acquisition, which refers to the ratio of the radioactivity of the imaging agent (radiolabeled drug) taken up by local tissues to the average injected activity of the whole body. It is specifically defined by Formula 1.
  • ROI is the region of interest defined in the image
  • Acitivity Concentration in ROI is the average radioactivity per unit volume in the region of interest
  • Injected Dose is the injected radioactivity
  • body weight is the weight of the irradiated body.
  • the radionuclide medical image is a PET image
  • the radioactively labeled boron-containing drug taken by the irradiated body is 18 F-BPA.
  • 18 F-BPA can also be replaced by other radioactive labels or other boron-containing drugs; it can also be a radioactively labeled non-boron-containing drug with a tumor cell affinity similar to that of the boron-containing drug, such as 18 F-FDG.
  • a method for generating a treatment plan based on a boron neutron capture therapy system comprises the following steps:
  • tissue-related information of the medical image data of the irradiated part a corresponding three-dimensional voxel prosthetic tissue model with tissue type and tissue density data is established, as shown in FIG6 , which specifically includes the following steps:
  • DICOM Digital Imaging and Communications in Medicine
  • DICOM data includes information such as irradiated body weight (Body Weight), injected drug dosage (Injection Dose), drug activity measurement time (Measure Time), imaging time (Scan Time), radionuclide half-life (Half Time), and drug type (Radiopharmaceutical). This information can be determined when the radionuclide medical imaging scan begins.
  • the information source can be manually input by the operator or automatically obtained or retrieved.
  • tissue type element composition
  • tissue density of each voxel unit.
  • It can be automatically defined based on the conversion relationship between CT image data and tissue type and tissue density; it can also be manually defined by the user, such as giving a specific tissue type and tissue density to each voxel unit within the boundary of the region of interest.
  • the boron concentration data corresponding to each voxel unit in the three-dimensional voxel prosthetic tissue model is given according to the boron concentration related information of the medical imaging data of the irradiated part.
  • the concentration of the boron-containing drug in each voxel unit can be clearly known according to the three-dimensional voxel prosthetic tissue model marked with the tissue boron concentration information. Then, when performing neutron irradiation simulation, the nuclear particle collision trajectory and energy distribution in the region of interest of the irradiated body can be more realistically reflected.
  • the boron concentration related information is obtained through the radionuclide medical imaging of the irradiated part.
  • the radioactively labeled boron-containing drug ingested by the irradiated body is used for radionuclide medical imaging.
  • the scanning and treatment planning module 30 assigns different boron concentrations to each voxel unit in the three-dimensional voxel prosthesis tissue model based on the radionuclide medical imaging data and the boron concentration information, as shown in FIG. 7 , and specifically includes the following steps:
  • Regions of interest were grouped based on standard uptake values
  • the above formula 1 can convert the 10 B information in each voxel in the region of interest defined in the PET image into SUV values for quantitative analysis, so as to obtain the maximum, minimum and average SUV values in the region of interest.
  • Medical staff grouped the SUV values into groups I. After grouping, the average SUV value of the i-th group was calculated using formula 2, which is as follows:
  • I is the number of groups, which is set to an even number in one embodiment of the present invention
  • SUV ROI,upper is the upper limit of the SUV value in the region of interest
  • SUV ROI,lower is the lower limit of the SUV value in the region of interest; wherein, the upper limit and lower limit of the SUV value in the region of interest are set based on the SUV value range in the region of interest, and will be adjusted based on grouping and normalization.
  • the system obtains the body parameters of the drug and the irradiated body according to the PET image tag (DICOM Tag), and obtains the drug uptake degree and its distribution information for the region of interest defined by the system user to determine the number of groups.
  • the distribution of the drug uptake degree is discrete, a larger number of groups is set; conversely, when the distribution of the drug uptake degree is uniform, a smaller number of groups is set.
  • the total number of 10 B atoms distributed in the region of interest remains unchanged before and after the SUV values in the region of interest are grouped. Based on this, the number of groups or the average SUV value is adjusted using Formula 3 to ensure that the total number of 10 B atoms after grouping is basically the same as the total number of 10 B atoms before grouping.
  • Formula 3 is as follows:
  • SUV ROI (V) is the SUV value of the Vth voxel in the region of interest
  • ⁇ V SUV ROI (V)dV is the total SUV value before grouping
  • Ni is the count of the i-th group
  • k is the normalization factor
  • It is the total value of SUV after grouping.
  • the number of groups I or the average SUV value is adjusted by the normalization factor k until the difference between the total number of 10 B atoms after grouping and the total number of 10 B atoms before grouping is within a preset range.
  • the preset range is 5%.
  • ⁇ is a constant conversion factor used to convert the SUV value to the corresponding number of 10 B atoms
  • i represents the group index
  • SUV ROI,upper is the upper limit of the SUV value in the region of interest
  • SUV ROI,lower is the lower limit of the SUV value in the region of interest
  • SUV ROI (V) is the SUV value of the Vth voxel in the region of interest.
  • a Monte Carlo simulation program (such as MCNP, Monte Carlo N Particle Transport Code) is used for simulation.
  • MCNP Monte Carlo N Particle Transport Code
  • the physical dose rate distribution of the three-dimensional voxel prosthetic tissue model at different irradiation angles is simulated, that is, the physical dose received by each voxel unit in the three-dimensional voxel prosthetic tissue model per unit time under the irradiation of the defined beam is simulated at different sampling irradiation angles, thereby obtaining the dose distribution.
  • Formula 5 is as follows:
  • NB10 (V) is the number of 10B atoms in the Vth voxel
  • RRB10 is the reaction rate of each 10B atom
  • Ecap is the energy released by the capture reaction of 10B atoms
  • Mass(V) is the mass of the Vth voxel (unit: kg)
  • ⁇ is a constant conversion factor
  • SUVROI (V) is the SUV value of the Vth voxel in the region of interest
  • the boron physical dose DB10 is in Gy.
  • the irradiation position and irradiation angle can be determined by a forward algorithm or a reverse algorithm.
  • the forward algorithm the irradiation position is determined at an external position and can be sampled and calculated in sequence at a fixed angle or distance interval, or by random sampling.
  • the beam angle can be set as the vector direction from the irradiation position to the tumor centroid or the deepest part of the tumor.
  • the reverse algorithm the starting position is determined within the tumor range, and the starting position can be a random point within the tumor centroid, the deepest part, or the tumor range, while the beam angle can be sampled randomly or at a specified interval.
  • the beam angle can also be screened, such as performing a beam angle evaluation to select a better irradiation angle or eliminating irradiation angles that cannot be implemented due to equipment interference.
  • the irradiation angle is optimized to generate a treatment plan:
  • the maximum dose, average dose or prescription dose of the region of interest is used as a constraint to obtain the irradiation time corresponding to the sampled irradiation angle, and the equivalent dose distribution of the three-dimensional voxel prosthetic tissue model under the sampled irradiation angle is obtained by using the irradiation time.
  • the dose-volume histogram (DVH), isodose curves, dose tables, etc. are used to evaluate the equivalent dose distribution calculated by simulating different irradiation angles and corresponding irradiation times in the three-dimensional voxel prosthesis tissue model, and to select a treatment plan that is feasible and meets the needs.
  • the treatment planning module 30 of the boron neutron capture therapy system groups the regions of interest based on the standard uptake value and assigns corresponding boron concentration data to each voxel unit through calculation, and then performs dose simulation in combination with medical imaging data and beam parameters to formulate a treatment plan, so that the distribution of boron atoms in the region of interest is more in line with the actual situation, which can improve the accuracy of model establishment and dose calculation, ensure the accuracy of the treatment plan, and thus ensure the treatment effect.
  • the boron concentration information is preset, and the treatment plan is further generated based on the preset boron concentration information.
  • the second embodiment of the present invention provides a boron neutron capture therapy system, including a neutron irradiation device 10, a treatment planning module 30 and a control module 40.
  • the neutron irradiation device 10 is used to generate a neutron beam and irradiate the irradiated body.
  • the treatment planning module 30 is used to determine at least a high-concentration drug absorption area and a low-concentration drug absorption area based on the region of interest, assign drug concentrations and evaluate dose distribution for the high-concentration drug area and the low-concentration drug area, and generate a treatment plan.
  • the control module 40 is used to control the neutron irradiation device 10 to execute the treatment plan.
  • the treatment planning module 30 includes a modeling module, a processing module, a dose assessment module and a treatment plan generation module.
  • the modeling module, the processing module, the dose assessment module and the treatment plan generation module are electrically connected in sequence, and data can be transmitted through the electrical connection.
  • the modeling module is used to establish a three-dimensional voxel tissue model based on medical image data. It is understandable that the boron neutron capture therapy system also includes an imaging device, which is used to obtain the medical image data required by the treatment planning module 30.
  • the medical image data is a fusion image data of the first image data and the second image data.
  • the first image data is image data that can display the contour of the tissue of the irradiated body.
  • the second image data is image data that can display the distribution of the drug taken into the irradiated body.
  • the second image data is especially radionuclide medical image data, and the drug taken or injected by the irradiated body contains a radioactive marker, so that the distribution of the drug in the irradiated body is displayed in the second image data, and the second image data contains marker parameters that can describe the distribution of the marker.
  • a single boron concentration is assigned to the lesion area. This requires high accuracy in the division of the region of interest, and the regions of interest divided according to different medical images are different. This difference will lead to inaccurate dose calculations. If a single boron concentration is assigned and the region of interest is divided using a single image data, the calculation results will be even more inaccurate.
  • the lesion area is divided according to the first image data, and the target area with high drug uptake is divided according to the second image data.
  • the lesion area is larger than the target area, it means that there is a part of the lesion area that has not obviously taken in the corresponding drug.
  • the lesion area is smaller than the target area, it means that too much drug is taken in the normal area. Both of the above situations will lead to deviations in dose calculations. Even when the lesion area is close to the target area, there will be differences in drug concentration in the two areas. Problems such as poor distribution uniformity distort the maximum and minimum doses in dose assessment.
  • the second embodiment uses the fused image to divide the region of interest, avoiding the corresponding defects of different image data, and can divide the region of interest according to the clear tissue contour and the distribution of the ingested drug, thereby improving the accuracy of dividing the region of interest.
  • the impact of the accuracy of the region of interest division on the dose calculation is improved, and the problem of inaccurate dose calculation caused by the traditional single boron concentration assignment is avoided, thereby further improving the accuracy of dose assessment.
  • the first image data is acquired by a first imaging device.
  • the first imaging device is a computed tomography (CT) device or a magnetic resonance (MR) device, which can be a conventional CT, an enhanced CT, a CTsim or a MR.
  • CT has a better imaging effect on bones
  • MR has a better imaging effect on soft tissues.
  • the first imaging device can especially use CTsim.
  • the image obtained by CTsim has a higher definition, which can improve the accuracy of image alignment and regional division in subsequent steps, as shown in Figure 9, which shows a preliminary lesion area delineated according to the CTsim image.
  • the first image data cannot display information data on drug distribution.
  • the irradiated body can either take or be injected with a drug containing a marker, or not take or be injected with a drug containing a marker.
  • the second image data is acquired by a second imaging device, and the second imaging device is particularly a radionuclide medical imaging acquisition device.
  • the second imaging device is a multi-mode imaging device, and the multi-mode imaging device includes at least a first mode unit and a second mode unit.
  • the first mode unit can acquire a second functional image of the imaging data containing marker parameters, and the second mode unit can obtain a second cross-sectional image.
  • One of the first mode unit and the second mode unit can acquire or generate a transformation matrix of the second functional image and the second cross-sectional image, and the transformation matrix can realize the registration and fusion of the second functional image and the second cross-sectional image.
  • the images of the same or different imaging modes are transformed using the transformation matrix so that their spatial positions and spatial coordinates are matched, and the two images are spatially registered using the characteristics of their respective imaging modes, and the registered image data are fused into a single image.
  • the multimodal imaging device may specifically be a combination of an emission computed tomography (ECT) device and other imaging devices, such as: a positron emission tomography (PET) device combined with CT to form PET-CT; a single-photon emission computed tomography (SPECT) device combined with CT to form SPECT-CT; or a positron emission tomography device combined with a nuclear magnetic resonance device to form PET-MR.
  • ECT emission computed tomography
  • other imaging devices such as: a positron emission tomography (PET) device combined with CT to form PET-CT; a single-photon emission computed tomography (SPECT) device combined with CT to form SPECT-CT; or a positron emission tomography device combined with a nuclear magnetic resonance device to form PET-MR.
  • PET emission computed tomography
  • SPECT single-photon emission computed tomography
  • the second imaging device may be the same imaging device as the first imaging device, and the imaging device may be a multi-modal imaging device, such as PET-CT, SPECT-CT or PET-MR, etc. Technicians may obtain the data required for the first imaging data and the second imaging data from the imaging data output by the multi-modal imaging device.
  • a multi-modal imaging device such as PET-CT, SPECT-CT or PET-MR, etc.
  • Technicians may obtain the data required for the first imaging data and the second imaging data from the imaging data output by the multi-modal imaging device.
  • the modeling module performs three-dimensional voxel tissue modeling based on the first image data or the fused image data, and can establish a The three-dimensional voxel tissue model of marker parameters, each voxel unit in the model has corresponding drug distribution parameters and marker parameters.
  • the processing module is used to define a region of interest based on a three-dimensional voxel tissue model. Based on the region of interest, at least a high-concentration drug absorption region and a low-concentration drug absorption region are determined, and the high-concentration drug absorption region and the low-concentration drug absorption region are grouped. The high-concentration drug absorption region is divided into at least one group, and the low-concentration drug absorption region is divided into at least two groups, and drug concentration is assigned to each group.
  • the processing module can delineate a region of interest based on the above-mentioned fused image data, and the region of interest includes the area of the lesion that needs to be irradiated.
  • the processing module can accurately and automatically delineate the required region of interest using the fused image data, as shown in FIG10 , FIG10 shows a fused image after the CTsim image and the PET image are fused, and the range marked by the red circle in FIG10 is the delineated region of interest.
  • the operator can operate the processing module 12 to divide the region of interest.
  • the division between the high concentration drug absorption region and the low concentration drug absorption region is based on a certain specified value characterizing the drug concentration, which is usually determined based on considerations of therapeutic benefit.
  • the high-concentration drug absorption area since the tissue in this area has a higher drug uptake rate, a higher concentration of drug distribution is formed.
  • the drug concentration of the voxel units in the high-concentration drug absorption area is greater than the drug concentration represented by the above-specified value.
  • the drug concentration distribution in the high-concentration drug absorption area is highly uniform. The results of assigning uniform drug concentration to this area and performing dose calculation are highly consistent with the actual received dose. Therefore, the high-concentration drug absorption area can be divided into at least one group.
  • the low-concentration drug absorption area since the tissue in this area has a lower drug uptake rate, a lower concentration of drug distribution is formed.
  • the drug concentration of the voxel units in the low-concentration drug absorption area is lower than the drug concentration represented by the above-specified value.
  • the drug concentration distribution range of the low-concentration drug absorption area is wide and the uniformity is poor. The result of directly assigning an overall uniform drug concentration to the area and performing dose calculation is quite different from the actual received dose. Therefore, the low-concentration drug absorption area needs to be divided into more groups to perform non-uniform drug concentration dose calculation to improve the accuracy and reliability of dose assessment.
  • the low-concentration drug absorption area can be divided into at least two groups. Furthermore, the number of groups divided into the high-concentration drug absorption area is less than the number of groups divided into the low-concentration drug absorption area.
  • the treatment planning module 30 is further used to define TBR as the ratio of the drug concentration in the region of interest to the drug concentration in the blood, and define TNR as the ratio of the drug concentration in the region of interest to the drug concentration in normal tissue.
  • the processing module divides the high-concentration drug absorption area and the low-concentration drug absorption area according to the value of TBR or TNR, and groups the high-concentration drug absorption area and the low-concentration drug absorption area according to the value of TBR or TNR, and the value of TBR or TNR is used as the above-mentioned specified value.
  • the processing module determines the region in the region of interest where the TBR is greater than or equal to the first specified value as a high concentration drug absorption region, or determines the region where the TNR is greater than or equal to the second specified value as a high concentration drug absorption region.
  • the processing module determines the region in the region of interest where the TBR is less than the first specified value or the TNR is less than the second specified value as a low concentration drug absorption region.
  • the drug taken or injected by the irradiated body is a boron drug.
  • concentration of boron drug taken up by normal tissue is lower than the boron concentration in the blood, that is, the TNR for the same region of interest is greater than the TBR, the first designated value is greater than or equal to 1.2, and the second designated value is greater than or equal to 1.5.
  • the drug taken or injected by the irradiated body is BPA, specifically 18 F-BPA, and the uptake of BPA by the human body is that the boron concentration of normal tissue uptake is similar to the boron concentration of blood, that is, for the same region of interest, TNR is equal to TBR, the first specified value is equal to 2.5, and the second specified value is equal to 2.5.
  • TBR has an Nth designated value
  • TNR has an Mth designated value
  • the Nth designated value and the Mth designated value divide the region of interest into N+1 or M+1 regions, wherein N and M are integers greater than or equal to 1.
  • the total number of divided regions, the number of regions divided by the high-concentration drug absorption region, and the number of regions divided by the low-concentration drug absorption region can all be determined by factors such as the type of drug, the uniformity of drug concentration distribution, the type of tumor to be treated, and the individual differences of the irradiated body.
  • the specific values of the Nth designated value and the Mth designated value are determined by factors such as the type of designated value (TBR or TNR), the maximum and minimum designated values of the region of interest, the type of drug, the type of tumor to be treated, and the individual differences of the irradiated body.
  • the processing module is used to divide the region of interest into three groups, wherein the high concentration drug absorption region is divided into one group, which is the first zone.
  • the low concentration drug absorption region is divided into two groups, which are the second zone and the third zone.
  • the region where the TBR of the low concentration drug absorption region is greater than or equal to the third specified value or the TNR is greater than or equal to the fourth specified value is the second zone, and the region where the TBR of the low concentration drug absorption region is less than the third specified value or the TNR is less than the fourth specified value is the third zone.
  • the third specified value is greater than 1.5 and less than or equal to 2.0, and the fourth specified value is equal to the third specified value.
  • the drug is BPA
  • the third specified value is equal to the fourth specified value and is equal to 2.0.
  • the drug uptake distribution can be observed and obtained. Since the label does not affect the pharmacokinetics of the drug itself, the distribution of the drug using the radionuclide label is quite reliable.
  • the embodiments described in this application are based on radionuclide medical imaging, such as PET imaging, to obtain TBR or TNR, and then group the regions of interest, so that the drugs injected into the irradiated body are radionuclide labeled drugs.
  • TBR or TNR can be obtained without medical imaging, and blood or tissue can be drawn to measure drug concentration.
  • the injected drugs can be ordinary drugs that are not labeled with radionuclides.
  • the treatment planning module 30 is also used to convert the drug concentration into a numerical value among the radioactivity of the marker, the radioactivity intensity of the marker, the number of atoms decayed per unit time, the effective count of the mutual destruction photons, and the standard uptake value obtained based on the medical imaging data for quantitative or semi-quantitative analysis, and obtain the quantitative or semi-quantitative parameters of the corresponding marker, which are recorded as the marker parameters, and the above-mentioned specified values are the marker parameters.
  • the imaging device can directly obtain the marker parameters from the second image data or the fused image data.
  • the radionuclide marker can be 18 F.
  • the standard uptake value SUV of each region can be obtained.
  • the TBR and TNR can be calculated by the following formula (1) and formula (2) respectively:
  • SUV i is the SUV value of the i-th voxel unit in the region of interest
  • SUV blood is the SUV value in the blood
  • SUV normal is the SUV value of normal tissue.
  • the processing module assigns drug concentration to each group of divided regions.
  • a uniform drug concentration assignment method is used for each group of regions. Specifically, based on the tumor volume of the Vth region, the TBR or TNR of each voxel unit in the region is averaged and calculated, and the calculation result is used as the average specified value. Based on the average specified value, the uniform drug concentration of the region is obtained as the basis for dose distribution evaluation.
  • the drug is a radionuclide-labeled boron drug
  • the treatment plan module 30 is used to convert the boron concentration NB10 into a standard uptake value (SUV) for quantitative analysis, as shown in the following formula 6:
  • N B10 (V) represents the number of 10 B atoms in the Vth region, i.e., the boron concentration
  • ⁇ is a constant conversion factor.
  • the processing module can automatically define or manually define the boron concentration of each voxel unit in the three-dimensional voxel tissue model according to the conversion relationship between the SUV value and the boron concentration, and the physical dose of boron in each voxel can be calculated based on the boron concentration.
  • the dose assessment module performs dose assessment based on drug concentration and irradiation parameters of the neutron beam, and the treatment plan generation module generates a treatment plan based on the result of the dose assessment.
  • the dose assessment module simulates the internal three-dimensional nuclear particle collision trajectory and energy distribution when the patient is irradiated by neutron beam in BNCT through the internal preset Monte Carlo simulation program, that is, it can simulate the physical dose rate distribution and calculate the equivalent dose rate distribution based on the physical dose rate distribution.
  • the irradiation parameters of the neutron beam (such as beam energy, intensity, radius, etc.) are defined in the Monte Carlo simulation program to simulate the dose rate per unit time received by each voxel unit in the three-dimensional voxel tissue model under the defined irradiation parameters.
  • Physical dose In the dose calculation of BNCT treatment, the main factors contributing to the dose are boron dose, neutron dose, etc.
  • BNCT dose DB ⁇ CBE+D n ⁇ RBE n +D ⁇ ⁇ RBE ⁇ (Formula 7)
  • BNCT dose is the total equivalent dose under neutron irradiation
  • DB is the physical dose of boron
  • CBE is the compound biological effect of unit concentration of boron-containing drugs
  • Dn is the physical dose of neutrons
  • RBEn is the relative biological effect of neutrons
  • D ⁇ is the physical dose of photons
  • RBE ⁇ is the relative biological effect of photons.
  • the equivalent dose distribution calculated by simulating a three-dimensional voxel tissue model can be evaluated by mathematical algorithms such as dose volume histogram (DVH), isodose curves, and dose tables.
  • DVDH dose volume histogram
  • FIG8 shows a schematic flow chart of a dose assessment method for a boron neutron capture therapy system according to a second embodiment of the present application.
  • the dose assessment method comprises the following steps:
  • Modeling Establishing a three-dimensional voxel tissue model based on the medical image data of the irradiated body.
  • the step of establishing a three-dimensional voxel tissue model based on the medical image data also includes: acquiring first image data; establishing a three-dimensional voxel tissue model based on the first image data.
  • the first image data is image data that can display the contour of the tissue of the irradiated body.
  • Delineating the region of interest defining the region of interest based on the three-dimensional voxel tissue model.
  • the step of defining the region of interest based on the three-dimensional voxel tissue model also includes: acquiring first image data; acquiring second image data; registering and aligning the first image data with the second image data to obtain fused image data; and delineating the region of interest based on the fused image data.
  • the first image data is CT or MRI
  • the second image data is radionuclide medical image data.
  • steps of establishing a three-dimensional voxel tissue model based on the first image data and obtaining the second image data and obtaining fused image data are in no particular order. It is understandable that a three-dimensional voxel tissue model can also be established based on fused image data.
  • Zoning and grouping based on the region of interest, at least a high-concentration drug absorption region and a low-concentration drug absorption region are determined, and the high-concentration drug absorption region and the low-concentration drug absorption region are grouped, wherein the high-concentration drug absorption region is divided into at least one group, and the low-concentration drug absorption region is divided into at least two groups, and drug concentration is assigned to each group.
  • the partitioning and grouping step also includes the following steps:
  • TBR or TNR Partitioning by TBR or TNR: define TBR as the ratio of the drug concentration in the region of interest to the drug concentration in the blood, and define TNR as the ratio of the drug concentration in the region of interest to the drug concentration in normal tissue; determine the region in which the TBR of the region of interest is greater than or equal to the first specified value or the region in which the TNR is greater than or equal to the second specified value as the high-concentration drug absorption region, and determine the region in which the TBR of the region of interest is less than the first specified value or the region in which the TNR is less than the second specified value as the low-concentration drug absorption region.
  • the designated value is determined according to the drug: if the drug is a boron drug, the first designated value is greater than or equal to 1.2, and the second designated value is greater than or equal to 1.5; if the drug is BPA, the first designated value is equal to the second designated value, which is 2.5.
  • the step of partitioning by TBR or TNR also includes: dividing the region of interest into three groups, wherein the high-concentration drug absorption region is divided into one group, which is the first zone; the low-concentration drug absorption region is divided into two groups, which are the second zone and the third zone, respectively, the region where the TBR of the low-concentration drug absorption region is greater than or equal to the third designated value or the TNR is greater than or equal to the fourth designated value is the second zone, the region where the TBR of the low-concentration drug absorption region is less than the third designated value or the TNR is less than the fourth designated value is the third zone, and the third designated value is equal to the fourth designated value, which is equal to 2.0.
  • the irradiated body is a patient with a brain tumor.
  • the tumor volume GTV anatomy of the patient is relatively large, and the volume of the region of interest is 155.9cc, that is, the GTV anatomy is 155.9cc.
  • the patient is injected with the boron drug 18 F-BPA, and the TBR range obtained from the image data is 0.70-5.95, as shown in Figure 11.
  • the first designated value is taken as 2.5, and the area with TBR ⁇ 2.5 is divided into a high-concentration drug absorption area and used as the first area.
  • the red area circled by the green line in Figure 11 is the first area; the area with TBR ⁇ 2.5 is divided into a low-concentration drug absorption area.
  • the third designated value is taken as 2.0, and the low-concentration drug absorption area is divided into a second area with 2.0 ⁇ TBR ⁇ 2.5 and a third area with TBR ⁇ 2.0.
  • the orange area circled by the yellow line in Figure 11 is the second area, and the green area circled by the red line is the third area.
  • Drug concentration assignment Based on the tumor volume GTV anatomy of the Vth region, the TBR or TNR of each voxel unit in the region is averaged to obtain the uniform boron concentration in the region.
  • the tumor volume GTV 1 in the first zone is 60.8cc
  • the average assigned value (i.e., average TBR) in the zone is 3.30 based on the TBR-volume histogram shown in Figure 12.
  • the tumor volume GTV 2 in the second zone is 63.0cc
  • the average TBR in the zone is 2.26 based on Figure 12.
  • the tumor volume GTV 3 in the third zone is 35.1cc
  • the average TBR in the zone is 1.67 based on Figure 12.
  • each of the above average TBRs corresponds to a boron concentration value.
  • Dose assessment is performed based on drug concentration and neutron beam irradiation parameters.
  • the step of dose assessment includes: calculating the irradiation dose based on the drug concentration and the irradiation parameters of the neutron beam.
  • the results of the non-uniform boron concentration distribution dose function calculated by the existing treatment planning system NeuMANTA were used as the control calculation group, and compared with the dose assessment results provided in the second embodiment.
  • the control group all boron concentrations of the GTV anatomy were grouped into 132 regions, and boron concentrations were assigned to the 132 regions, which is equivalent to dividing the GTV anatomy into 132 regions for uniform boron concentration distribution dose calculation.
  • the GTV anatomy is divided into 3 regions for uniform boron concentration distribution dose calculation.
  • the dose calculation time of the second embodiment is shortened by nearly 80% compared with that of the control group. This is because in the calculation of the control group, due to the small difference in boron concentration between some of the 132 regions, the difference in boron concentration has little effect on the dose calculation, but increases the calculation time and occupies a higher memory.
  • the partitioning and grouping method of the second embodiment of the present application While ensuring that the dose results have high credibility and high accuracy, the dose calculation time is greatly reduced, and thus the time used for treatment plan formulation is reduced, and the requirements and dependence of the treatment plan system 10 on hardware devices are also reduced, thereby improving the convenience of the treatment process.
  • the GTV anatomy dose results and differences of the second embodiment of the present application and the control group are shown in Figure 13 and the following table:
  • D max is the maximum dose obtained in the simulated treatment calculation of the irradiated body
  • D min is the minimum dose obtained in the simulated treatment calculation of the irradiated body
  • D mean is the average dose obtained in the simulated treatment calculation of the irradiated body
  • D 80 is the dose obtained at 80% of the volume of the lesion, in Gy-Eq.
  • the solid line represents the dose-volume histogram of the method of the second embodiment of the present application
  • the dotted line represents the dose-volume histogram of the control group method.
  • the abscissa Dose (Gy-Eq) is the irradiation dose
  • the ordinate Volume (%) is the percentage of the lesion volume.
  • the DVH distributions of the two methods are quite consistent. Specifically, the deviation of the results calculated in accordance with the method of the second embodiment of the present application from the calculation results of the non-uniform boron concentration at D min , D mean and D 80 does not exceed 15%, especially at D mean and D 80 , the deviation between the calculation results of the uniform boron concentration and the calculation results of the non-uniform boron concentration does not exceed 5%.
  • the actual treatment dose is often based on a low dose as a reference, such as using the dose D 80 obtained by 80% of the volume of the lesion as a reference, thereby ensuring that the lesion can obtain a sufficient prescription dose while reducing the impact on the patient's health.
  • D 80 as the evaluation standard
  • the calculation results of the embodiment of the present application have a smaller deviation than the calculation results of the non-uniform boron concentration of the control, so the method of the present application can save calculation time while ensuring the accuracy of dose calculation.
  • steps in the flowcharts involved in the above-mentioned embodiments can include multiple steps or multiple stages, and these steps or stages are not necessarily executed at the same time, but can be executed at different times, and the execution order of these steps or stages is not necessarily carried out in sequence, but can be executed in turn or alternately with other steps or at least a part of the steps or stages in other steps.

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Abstract

一种硼中子捕获治疗系统(100)及其工作方法，硼中子捕获治疗系统(100)包括：中子束照射装置(10)，用于产生中子束并照射被照射体；治疗计划模块(30)，用于对三维体素假体组织模型中的每一体素单元进行硼浓度赋值并生成治疗计划；及控制模块(40)，用于根据治疗计划控制中子束照射装置(10)执行照射。治疗计划模块(30)给每一体素单元赋予相应的硼浓度数据，再结合医学影像数据进行剂量模拟以制定治疗计划，使得硼原子在感兴趣区域内的分布更加符合实际情况，能够提高模型建立及剂量计算的精确性，确保了治疗计划的准确度，从而保证了治疗效果。

Description

硼中子捕获治疗系统及其治疗计划生成方法 技术领域
本申请涉及放射治疗技术领域，特别是涉及一种硼中子捕获治疗系统及其治疗计划生成方法。
背景技术
随着原子科学的发展，例如钴六十、直线加速器、电子射束等，放射线治疗已成为癌症治疗的主要手段之一。然而传统光子或电子治疗受到放射线本身物理条件的限制，在杀死肿瘤细胞的同时，也会对射束途径上大量的正常组织造成伤害；另外由于肿瘤细胞对放射线敏感程度的不同，传统放射治疗对于较具抗辐射性的恶性肿瘤(如：多行性胶质母细胞瘤(glioblastoma multiforme)、黑色素细胞瘤(melanoma))的治疗成效往往不佳。
为了减少对肿瘤周边正常组织的辐射伤害，化学治疗(chemotherapy)中的标靶治疗概念便被应用于放射线治疗中；而针对高抗辐射性的肿瘤细胞，目前也积极发展具有高相对生物效应(relative biological effectiveness,RBE)的辐射源治疗方法，如质子治疗、重粒子治疗、中子捕获治疗等。其中，中子捕获治疗中的硼中子捕获治疗借由含硼药物在肿瘤细胞的特异性集聚，配合精准的中子射束调控，提供了一种比传统放射线治疗更好的癌症治疗选择。
硼中子捕获治疗(Boron Neutron Capture Therapy,BNCT)是利用含硼(10B)药物对热中子具有高捕获截面的特性，借由10B(n,α)7Li中子捕获及核分裂反应产生4He和7Li两个重荷电粒子，两重荷电粒子的平均能量约为2.33MeV，具有高线性转移(Linear Energy Transfer,LET)、短射程特征，α粒子的线性能量转移与射程分别为150keV/μm、8μm，而7Li重荷粒子则为175keV/μm、5μm，两粒子的总射程约相当于一个细胞大小，因此对于生物体造成的辐射伤害能局限在细胞层级，当含硼药物选择性地聚集在肿瘤细胞中，搭配适当的中子射源，便能在不对正常组织造成太大伤害的前提下，达到局部杀死肿瘤细胞的目的。
在硼中子捕获治疗过程中，由于对被照射体进行辐射线照射治疗的中子束辐射线较强，需要精确控制对被照射体实施的照射剂量以在达到较好的治疗效果的同时尽量降低辐射线对被照射体造成的辐射损伤，因此，治疗计划的制定的准确度至关重要。三维模型能够模拟人体在一定辐射条件下的吸收剂量以帮助医生制定治疗计划，常常需要利用计算机技术对医学影像数据进行各种处理建立精确的蒙特卡罗软件需要的晶格模型，并结合蒙特卡罗软件进行模拟计算。在中子捕获治疗领域根据医学影像数据建立蒙特卡罗软件所需的晶格模型并进行剂量计算和评估时，需要在模型中定义每个晶格反映的生物体基本信息，如组织种类、硼浓度信息等，信息的准确性和精确度决定了剂量计算结果的可靠度。而通常硼浓度信息是根据 血样检验或切片检验获得样本的硼浓度数据，以此推算相应的组织和肿瘤硼浓度，从而在对应的模型区域中给定区域硼浓度值，这样给定的硼浓度信息没有考虑生物体内真实的硼药分布及硼药随时间的代谢情况，进而影响剂量计算结果的可靠度，导致治疗计划的准确度较低而无法达到满意的治疗效果。
发明内容
基于此，有必要针对上述技术问题，提供一种能够保证治疗效果的硼中子捕获治疗系统及其治疗计划生成方法。
本发明一方面提供一种硼中子捕获治疗系统，其包括：中子束照射装置，用于产生中子束并照射被照射体；治疗计划模块，用于对三维体素假体组织模型中的每一体素单元进行硼浓度赋值并生成治疗计划；及控制模块，用于根据所述治疗计划控制所述中子束照射装置执行照射。
进一步的，所述治疗计划模块基于标准摄取值对三维体素假体组织模型中的感兴趣区域进行分组并计算每一组的标准摄取值的平均值。
进一步的，每一组标准摄取值SUV的平均值采用公式二进行计算：
其中，I为组数，本发明一实施例中设为偶数、SUVROI,upper为感兴趣区域内的SUV值的上限值、SUVROI,lower为感兴趣区域内的SUV值的下限值。
进一步的，所述组数I大于等于10小于等于500。
进一步的，所述组数I大于等于10小于等于100。
进一步的，所述组数I等于40、44、50、54或60。
进一步的，所述治疗计划模块基于归一化因子k调整组数I或者SUV平均值，归一化因子k采用公式三进行计算：
其中，SUVROI(V)为感兴趣区域内中第V个体素SUV值、∫VSUVROI(V)dV为未分组前SUV总值、Ni为第i组的计数、k为归一化因子、为分组后SUV总值。
进一步的，所述治疗计划模块根据公式四确定感兴趣区域中每一体素内的硼浓度 NB10,group(V)，公式四如下：
其中，ξ为常数转换因子，其用于将SUV值转换为相应的10B原子数量、i表示组群索引、SUVROI(V)为感兴趣区域中第V个体素SUV值。
本发明第二方面提供一种硼中子捕获治疗系统，包括中子照射装置，用于产生中子束并照射被照射体；治疗计划模块，用于基于所述被照射体的感兴趣区域至少确定高浓度药物吸收区域和低浓度药物吸收区域，对所述高浓度药物吸收区域和所述低浓度药物吸收区域进行药物浓度赋值和剂量评估，生成治疗计划；控制模块，用于控制所述中子照射装置执行所述治疗计划。
进一步地，所述治疗计划模块包括：
建模模块，用于基于所述被照射体的医学影像数据建立三维体素组织模型；
处理模块，用于基于所述三维体素组织模型定义感兴趣区域，基于所述感兴趣区域至少确定高浓度药物吸收区域和低浓度药物吸收区域，并将所述高浓度药物吸收区域和所述低浓度药物吸收区域进行分组，其中，所述高浓度药物吸收区域至少分为一组，所述低浓度药物吸收区域至少分为两组，每组进行药物浓度赋值；
剂量评估模块，基于所述药物浓度和所述中子束的照射参数进行剂量评估；
治疗计划生成模块，基于所述剂量评估的结果生成治疗计划。
进一步地，所述治疗计划模块，还用于定义TBR为所述感兴趣区域的药物浓度与血液中药物浓度的比值，定义TNR为所述感兴趣区域的药物浓度与正常组织中药物浓度的比值；
所述处理模块，用于确定所述感兴趣区域的TBR大于或等于第一指定值的区域或TNR大于或等于第二指定值的区域为所述高浓度药物吸收区域，并确定所述感兴趣区域的TBR小于所述第一指定值的区域或TNR小于所述第二指定值的区域为所述低浓度药物吸收区域。
进一步地，所述药物为硼药，当正常组织摄取硼药浓度低于血液硼浓度，即对于同一感兴趣区域的TNR大于TBR，所述第一指定值大于或等于1.2，所述第二指定值大于或等于1.5。
进一步地，所述药物为BPA，人体对于BPA的摄取情况为正常组织摄取硼浓度与血液硼浓度相近，即对于同一感兴趣区域的TNR等于TBR，所述第一指定值等于2.5，所述第二指定值等于2.5。
进一步地，所述药物为放射线核素标记的18F-BPA。
进一步地，所述处理模块，用于将所述感兴趣区域分为三组，其中，将所述高浓度药物 吸收区域分为一组，为第一区；将所述低浓度药物吸收区域分为两组，分别是第二区和第三区，其中，所述低浓度药物吸收区域的TBR大于或等于第三指定值或TNR大于或等于第四指定值的区域为第二区，所述低浓度药物吸收区域的TBR小于第三指定值或TNR小于第四指定值的区域为第三区，所述第三指定值大于1.5且小于等于2.0，所述第四指定值等于所述第三指定值。
进一步地，所述第三指定值等于所述第四指定值，等于2.0。
进一步地，所述药物为放射性核素标记药物，所述治疗计划系统，还用于将所述药物浓度转化为基于医学影像数据获取的标记物放射性活度、标记物放射性强度、单位时间内衰变的原子数、互毁光子的有效计数以及标准摄取值中的一个数值进行定量或半定量分析。
进一步地，所述药物为放射性核素标记的硼药，所述治疗计划系统，用于将所述药物浓度转化为标准摄取值SUV进行定量分析，
其中，NB10(V)表示第V个区域的10B原子的数量，ξ为常数转换因子，为感兴趣区域中第V个区域的SUV平均值。
本发明第三方面提供一种硼中子捕获治疗系统的治疗计划生成方法，其包括以下步骤：建立带有组织种类、组织密度数据的三维体素假体组织模型；对三维体素假体组织模型中的每一体素单元进行硼浓度赋值；获取剂量分布；根据计算结果对照射角度进行优选生成治疗计划。
进一步的，所述建立带有组织种类、组织密度数据的三维体素假体组织模型的步骤包括：读取医学影像数据；建立三维医学影像体素模型；定义感兴趣区域的边界；定义每一体素单元的组织种类(元素组成)、组织密度。
进一步的，所述对三维体素假体组织模型中的每一体素单元进行硼浓度赋值的步骤包括：基于标准摄取值对感兴趣区域进行分组；确定感兴趣区域中每一体素内的硼浓度。
进一步的，所述对感兴趣区域进行分组的步骤包括：通过公式一将影像中感兴趣区域内每一体素中的10B信息可转换为SUV值的步骤，公式一如下：
其中，ROI为在影像中定义的感兴趣区域、Acitivity Concentration in ROI为感兴趣区域内每单位体积的平均放射性活度、Injected Dose为注射的放射性活度、body weight为被照射体的体重。
进一步的，对感兴趣区域进行分组的步骤具体为：通过归一化因子k调整组数I或者SUV 平均值。
进一步的，所述归一化因子k采用如下公式四进行计算：
其中，SUVROI(V)为感兴趣区域内中第V个体素SUV值、∫VSUVROI(V)dV为未分组前SUV总值、Ni为第i组的计数、k为归一化因子、为分组后SUV总值、为分组后第i组的SUV平均值，采用公式二进行计算：
其中，I为组数。
进一步的，感兴趣区域内每一体素的内硼浓度NB10,group(V)采用公式四进行计算：
其中，ξ为常数转换因子，其用于将SUV值转换为相应的10B原子数量、i表示组群索引、SUVROI(V)为感兴趣区域中第V个体素SUV值。
本发明第四方面提供一种硼中子捕获治疗系统的治疗计划生成方法，包括：基于被照射体的医学影像数据建立三维体素组织模型；基于所述三维体素组织模型定义感兴趣区域；基于所述感兴趣区域至少确定高浓度药物吸收区域和低浓度药物吸收区域，将所述高浓度药物吸收区域和所述低浓度药物吸收区域进行分组，其中，所述高浓度药物吸收区域至少分为一组，所述低浓度药物吸收区域至少分为两组，每组进行药物浓度赋值；基于所述药物浓度和中子束的照射参数进行剂量评估，获取剂量分布；根据计算结果对照射角度进行优选生成治疗计划。
进一步地，所述基于所述感兴趣区域至少确定高浓度药物吸收区域和低浓度药物吸收区域的步骤包括：定义TBR为所述感兴趣区域的药物浓度与血液中药物浓度的比值，定义TNR为所述感兴趣区域的药物浓度与正常组织中药物浓度的比值；确定所述感兴趣区域的TBR大于或等于第一指定值的区域或TNR大于或等于第二指定值的区域为所述高浓度药物吸收区域，确定所述感兴趣区域的TBR小于第一指定值的区域或TNR小于第二指定值的区域为所 述低浓度药物吸收区域。
进一步地，所述药物为硼药，所述第一指定值大于或等于1.2，所述第二指定值大于或等于1.5。
进一步地，所述药物为BPA，所述第一指定值与第二指定值相等，为2.5。
进一步地，所述药物为放射线核素标记的18F-BPA。
进一步地，将感兴趣区域分成三组，其中，将所述高浓度药物吸收区域分为一组，为第一区；将所述低浓度药物吸收区域分为两组，分别是第二区和第三区，所述低浓度药物吸收区域的TBR大于或等于第三指定值或TNR大于或等于第四指定值的区域为第二区，所述低浓度药物吸收区域的TBR小于第三指定值或TNR小于第四指定值的区域为第三区，所述第三指定值与第四指定值相等，所述第三指定值大于1.5小于等于2.0。
进一步地，所述第三指定值等于所述第四指定值，等于2.0。
进一步地，所述药物为放射性核素标记的硼药，将所述药物浓度转化为标准摄取值SUV进行定量分析，
其中，NB10(V)表示第V个区域的10B原子的数量，ξ为常数转换因子，为感兴趣区域中第V个区域的SUV平均值。
进一步地，所述定义感兴趣区域的步骤包括：获取所述被照射体的第一影像数据；获取所述被照射体的第二影像数据；将所述第一影像数据与所述第二影像数据进行配准对位，获得融合影像数据；基于所述融合影像数据划定所述感兴趣区域。
进一步地，所述第一影像数据为CT或MRI，所述第二影像数据为放射性核素医学影像数据。
本发明第一、第三方面提供的硼中子捕获治疗系统治疗计划模块给每一体素单元赋予相应的硼浓度数据，再结合医学影像数据进行剂量模拟以制定治疗计划，使得硼原子在感兴趣区域内的分布更加符合实际情况，能够提高模型建立及剂量计算的精确性，确保了治疗计划的准确度，从而保证了治疗效果。
本发明第二、第四方面提供的硼中子捕获治疗系统及其剂量评估方法，将感兴趣区域至少划分为高浓度药物吸收区域和低浓度药物吸收区域，避免了过多分组群化时大量的硼浓度数值增加蒙特卡罗模拟计算时间的问题，也避免了单一硼浓度赋值导致的计算可靠度不足的问题；同时，通过提高剂量评估的准确度与可信度，进一步地优化治疗计划。本申请既能保证剂量计算的准确性，确保病灶范围获得足够处方剂量，又能显著地降低蒙特卡罗模拟计算 量，缩短计算时间，使得更快速、准确地生成治疗计划，提高了治疗系统的运行效率。
附图说明
图1是硼中子捕获反应示意图。
图2是10B(n,α)7Li中子捕获核反应方程式。
图3是本发明实施例的中子捕获治疗系统的框图。
图4是本发明实施例中的中子照射装置的结构示意图。
图5是本发明一实施例种治疗计划生成方法的流程图。
图6是本发明一实施例中建立三维体素假体组织模型的方法的流程图。
图7是本发明一实施例中给定三维体素假体组织模型中每一体素单元的硼浓度数据的方法的流程图。
图8是本发明另一实施例中的硼中子捕获治疗剂量评估方法的流程示意图。
图9是本发明另一实施例中的CTsim影像及病灶区域的示意图。
图10是本发明另一实施例中的融合影像及感兴趣区域的示意图。
图11是本发明另一实施例中的感兴趣区域的分区示意图。
图12是本发明另一实施例中的感兴趣区域的TBR-体积直方图。
图13是本发明另一实施例中与对照组的剂量-体积直方图对比示意图。
附图标号说明：
硼中子捕获治疗系统100、中子束照射装置10、中子产生装置11、治疗台12、影像获取模块20、治疗计划模块30、控制模块40；中子照射装置100、辐射发生装置110、加速器111、射束传输装置112、射束整形体120、准直器126、反射体121、缓速体122、热中子吸收体123、辐射屏蔽体124、射束通道125。
具体实施方式
为了使本申请的目的、技术方案及优点更加清楚明白，以下结合附图及实施例，对本申请进行详细说明。应当理解，此处描述的具体实施例仅仅用以解释本申请，并不用于限定本申请。
作为一种优选地，以中子捕获治疗系统及其治疗计划生成方法为本发明的实施例。下面将简单介绍一下中子捕获治疗，尤其是硼中子捕获治疗。
硼中子捕获治疗(Boron Neutron Capture Therapy,BNCT)是利用含硼(10B)药物对热中子具有高捕获截面的特性，借由10B(n,α)7Li中子捕获及核分裂反应产生4He和7Li两个重荷电粒子。参照图1和图2，其分别示出了硼中子捕获反应的示意图和10B(n,α)7Li中子捕获核反应方程式，两荷电粒子的平均能量约为2.33MeV，具有高线性转移和短射程特征，α粒子的 线性能量转移量与射程分别为150keV/μm、8μm，而7Li重荷粒子则为175keV/μm、5μm，两粒子的总射程约相当于一个细胞大小，因此对于生物体造成的辐射伤害能局限在细胞层级，当含硼药物选择性地聚集在肿瘤细胞中，搭配适当的中子射源，便能在不对正常组织造成太大伤害的前提下，达到局部杀死肿瘤细胞的目的。
蒙特卡罗方法能够对辐照目标内部三维空间核粒子碰撞轨迹和能量分布进行精确模拟，在硼中子捕获治疗中，为了模拟人体在一定辐射条件下的吸收剂量以帮助医生制定治疗计划，常常需要利用计算机技术对医学影像进行各种处理以建立精确的蒙特卡罗软件需要的晶格模型，并结合蒙特卡罗软件进行模拟计算最终得到治疗计划。医学影像数据可以为核磁共振成像(Magnetic Resonance Imaging,MRI)、电子计算机断层扫描(Computed Tomography,CT)、正电子发射型计算机断层扫描(Positron Emission Tomography,PET)、PET-CT或X射线成像(X-Ray imaging)。但本领域技术人员熟知地，还可以使用其他的医学影像数据，只要该医学影像数据能够被转换成三维体素假体组织模型，就能够应用于本发明揭示的放射治疗系统及其治疗计划生成方法中。
参照图3所示，本发明一实施例的硼中子捕获治疗系统100包括中子束照射装置10、影像获取模块20、治疗计划模块30和控制模块40。中子束照射装置10包括中子产生装置11和治疗台12，中子产生装置11用于在照射治疗时产生治疗用中子束N并照射到治疗台12上摄入含硼(10B)药物的被照射体进行治疗。治疗前，治疗计划模块30根据被照射体被照射部位的医学影像数据和中子产生装置11产生的治疗用中子束N的参数等信息生成治疗计划。照射治疗时，控制模块40从治疗计划模块30调取当前被照射体对应的治疗计划，并根据治疗计划控制中子束照射装置10执行照射。本实施例中，治疗计划模块30用于生成治疗计划的治疗用中子束N的参数是基于辐射源参数生成的中子束模型。
参考图4所示，中子照射装置100包括辐射发生装置110和射束整形体120。辐射发生装置110包括加速器111、射束传输装置112和靶T，加速器111对带电粒子(如质子、氘核等)进行加速，产生如质子线的带电粒子线P，带电粒子线P照射到靶T并与靶T作用产生中子线(中子束)N，靶T优选为金属靶材，本发明的实施例中优选采用锂金属制成的靶材。但是本领域技术人员熟知的，靶的材料也可以由锂、铍之外的金属材料制成，例如由钽(Ta)或钨(W)等形成；靶可以为圆板状，也可以为其他固体形状，也可以使用液状物(液体金属)。
射束整形体120靠近被照射体M的一端具有用于汇聚中子束的准直器126。射束整形体120调整中子束的射束品质，辐射发生装置20产生的中子束N依次经过射束整形体120的中子束从射束出口127照射向被照射体M。准直器126用以汇聚中子束，使中子束在进行治疗 的过程中具有较高的靶向性。可以理解，本实施例也可以不具有准直器126，射束从射束整形体120出来后直接照射向被照射体M。
射束整形体120进一步包括反射体121、缓速体122、热中子吸收体123、辐射屏蔽体124和射束通道125，辐射发生装置110生成的中子由于能谱很广，除了超热中子满足治疗需要以外，需要尽可能的减少其他种类的中子及光子含量以避免对操作人员或被照射体造成伤害，因此从靶T出来的中子需要经过缓速体2212将其中的快中子能量(＞10keV)调整到超热中子能区(0.5eV-10keV)并尽可能减少热中子(＜0.5eV)，缓速体2212由与快中子作用截面大、超热中子作用截面小的材料制成，优选D2O、AlF3、FluentalTM、CaF2、Li2CO3、MgF2和Al2O3中的至少一种；反射体121包围缓速体122，并将穿过缓速体122向四周扩散的中子反射回中子射束N以提高中子的利用率，由具有中子反射能力强的材料制成，优选Pb或Ni中的至少一种；缓速体122后部有一个热中子吸收体123，由与热中子作用截面大的材料制成，优选Li-6，用于吸收穿过缓速体122的热中子以减少中子束N中热中子的含量，避免治疗时与浅层正常组织造成过多剂量，可以理解，热中子吸收体123也可以是和缓速体一体的，缓速体的材料中含有Li-6；辐射屏蔽体124用于屏蔽从射束通道125以外部分渗漏的中子和光子，辐射屏蔽体124的材料包括光子屏蔽材料和中子屏蔽材料中的至少一种，作为一种优选实施例，辐射屏蔽体124的材料包括光子屏蔽材料铅(Pb)和中子屏蔽材料聚乙烯(PE)。射束出口127设置在射束通道125后部，从射束出口127出来的超热中子束向被照射体照射，经浅层正常组织后被缓速为热中子到达被照射体M的肿瘤细胞。照射治疗时，控制模块20从治疗计划系统10中调取当前患者对应的治疗计划，并根据治疗计划控制中子照射装置100的照射。
本发明中，被照射体在治疗前需摄入放射性标记的含硼(10B)药物并通过放射性核素医学影像(如PET)获得硼(10B)浓度相关信息，即被照射体被照射部位的医学影像数据包括组织相关信息和硼浓度相关信息。具体的，放射性核素医学影像扫描设备利用放射性核素衰变产生的正电子与组织中的电子相遇发生正负电子对湮灭反应，此时用光电倍增管(PMT)等检测器便可以检测经湮灭反应发射出来的伽马射线，之后计算机形成反映正电子放射性同位素分布的横截面图像，从而得到硼浓度相关信息。一实施例中，采用18F-BPA-PET作为标记物进行扫描，将影像每一晶格的原始数据为18F衰变释出的正子与电子互毁作用产生光子的计数率转换为PET影像每一晶格的影像晶格强度作为医学影像数据的输出，又18F标志于BPA，因此PET影像上的原始数据可做为10B量化的依据。可以理解，如采用放射性标记的与含硼药物的肿瘤细胞亲和性近似的非含硼药物进行放射性核素医学影像扫描，影像上的原始数据也可同样做为10B量化的依据。
标准摄取值(Standard Uptake Value,SUV)为放射性核素医学影像采集的半定量指标，指局部组织摄取的显像剂(放射性标记的药物)的放射性活度与全身平均注射活度的比值，其通过公式一具体定义。
其中，ROI为在影像中定义的感兴趣区域、Acitivity Concentration in ROI为感兴趣区域内每单位体积的平均放射性活度、Injected Dose为注射的放射性活度、body weight为被照射体的体重。
第一实施例中，放射性核素医学影像为PET影像，被照射体摄入的放射性标记的含硼药物为18F-BPA。可以理解，18F-BPA还可以替换为其他放射性标记或其他含硼药物；也可以为放射性标记的与含硼药物的肿瘤细胞亲和性近似的非含硼药物，如18F-FDG。
参照图5所示，基于硼中子捕获治疗系统提供一种治疗计划生成方法，其包括以下步骤：
建立带有组织种类、组织密度数据的三维体素假体组织模型：
根据被照射部位的医学影像数据的组织相关信息建立对应的带有组织种类、组织密度数据的三维体素假体组织模型，参照图6所示，具体包括以下步骤：
读取医学影像数据；医学影像数据通常采用DICOM(Digital Imaging and Communications in Medicine)格式，DICOM数据中包括被照射体体重(Body Weight)、施打药物药量(Injection Dose)、药物活性测量时间(Measure Time)、造影时间(Scan Time)、放射性核素半衰期(Half Time)、药物种类(Radiopharmaceutical)等信息，这些信息在开始进行放射性核素医学影像扫描时即可以确定，信息来源可以是操作者手动输入的，也可以是自动获得或调取的。
建立三维医学影像体素模型；
定义感兴趣区域的边界；
定义每一体素单元的组织种类(元素组成)、组织密度。
可以根据CT影像数据与组织种类、组织密度之间的转换关系自动定义；也可以是用户手动定义，如为每个感兴趣区域的边界内的体素单元给定一个特定的组织种类和组织密度。
对三维体素假体组织模型中的每一体素单元进行硼浓度赋值：
根据被照射部位的医学影像数据的硼浓度相关信息给定三维体素假体组织模型中每一体素单元相应的硼浓度数据，根据标记有组织硼浓度信息的三维体素假体组织模型能够可清楚地知道各个体素单元内的含硼药物浓度，然后进行中子照射模拟时，能够更加真实地反应出被照射体的感兴趣区域内核粒子碰撞轨迹和能量分布。硼浓度相关信息通过被照射部位的放射性核素医学影像获得，被照射体摄入放射性标记的含硼药物用于进行放射性核素医学影像 扫描，治疗计划模块30基于放射性核素医学影像数据与硼浓度信息给三维体素假体组织模型中每一体素单元赋予不同的硼浓度，参照图7所示，具体包括以下步骤：
基于标准摄取值对感兴趣区域进行分组；
通过上述公式一能够将PET影像中定义的感兴趣区域内每一体素中的10B信息可转换为SUV值进行定量分析，从而可获得感兴趣区域内最大、最小和平均SUV值，医护人员将SUV值进行群化分为I组，分组后第i组的SUV平均值采用公式二计算得到，公式二如下：
其中，I为组数，本发明一实施例中设为偶数、SUVROI,upper为感兴趣区域内的SUV值的上限值、SUVROI,lower为感兴趣区域内的SUV值的下限值；其中，感兴趣区域内的SUV值的上限值和下限值是基于感兴趣区域内的SUV值范围设定的，会基于群化和归一化调整。
当感兴趣区域由由M种材料组成时，进行分组后，使用材料总数Mtotal＝M*I，若I过大则运算过程较为耗时，而I过小，则无法真实反映感兴趣区域内硼的实际分布。系统根据PET影像卷标(DICOM Tag)获得药物和被照射体的体型参数，针对系统用户定义的感兴趣区域获得药物摄取程度及其分布信息以确定分组的组数，当摄取药物程度分布离散，则设定较多的组数；反之，当摄取药物程度分布均匀，则设定较少的组数。，通常，I∈【10,500】，优选的，I∈【10,100】，更优选的，I为40、44、50、54或60。
原则上，对感兴趣区域内的SUV值进行群化分组前后，感兴趣区域内分布的10B原子总数不变，基于此，采用公式三调整组数或SUV平均值，保证分组后10B原子总数与分组前10B原子总数基本一致，公式三如下：
其中，SUVROI(V)为感兴趣区域内中第V个体素SUV值、∫VSUVROI(V)dV为未分组前SUV总值、Ni为第i组的计数、k为归一化因子、为分组后SUV总值。
通过归一化因子k调整组数I或者SUV平均值，直到分组后10B原子总数与分组前10B原子总数之间的差值在预设范围内，一实施例中，预设范围为5％。
可以理解的是，k用于调整组数I时，SUV平均值随之发生改变，k用于调整SUV平均值时，组数I随之发生改变。
确定感兴趣区域中每一体素内的硼浓度；
感兴趣区域内每一体素的内10B原子数NB10,group(V)采用公式四进行计算，公式四如下：
其中，ξ为常数转换因子，其用于将SUV值转换为相应的10B原子数量、i表示组群索引、SUVROI,upper为感兴趣区域内的SUV值上限值、SUVROI,lower为感兴趣区域内的SUV值的下限值、SUVROI(V)为感兴趣区域中第V个体素SUV值。
获取剂量分布：
对三维体素假体组织模型中感兴趣区域的每一体素定义了硼浓度(即硼原子数)、密度等信息后，采用蒙特卡罗模拟程序(如MCNP，Monte Carlo N Particle Transport Code)进行模拟，通过对不同照射角度取样，模拟三维体素假体组织模型在不同照射角度的物理剂量率分布，即分别模拟在不同取样照射角度下，三维体素假体组织模型中每一体素单元在所定义的射束的照射下单位时间所接收的物理剂量，从而得到剂量分布情况，假设俘获反应产生的4He和7Li当场沉积，则每一体素内的硼的物理剂量DB10采用公式五进行计算，公式五如下：
其中，NB10(V)表示第V个体素的10B原子的数量、RRB10为每个10B原子原子的反应率、Ecap为10B原子发生捕获反应所释放的能量、Mass(V)第V个体素的质量(单位：kg)、ξ为常数转换因子、SUVROI(V)为感兴趣区域中第V个体素SUV值，硼物理剂量DB10单位为Gy。
取样时需要确定射束的照射位置及照射角度，照射位置与照射角度的确定可以是顺向算法或逆向算法，顺向算法中是将照射位置决定于体外位置并可依固定角度或距离间隔依序取样计算，也可以透过随机取样的方式进行；射束角度的部分，则可设定为照射位置至肿瘤质心或肿瘤最深处的向量方向；逆向算法中，则是将起始位置决定于肿瘤范围内，其起始位置可以是肿瘤质心、最深处或肿瘤范围内随机取点，而射束角度则可以利用随机取样或依指定间隔取样的方式进行。取样时还可以对射束角度进行筛选，如进行射束角度评价选择较优的照射角度或剔除因设备干涉无法实施的照射角度。
根据计算结果对照射角度进行优选生成治疗计划：
以感兴趣区域的最大剂量、平均剂量或处方剂量等作为约束条件求得取样的照射角度对应的照射时间，以该照射时间获得取样的照射角度下三维体素假体组织模型的等效剂量分布， 然后采用剂量体积直方图(DVH)、等剂量曲线、剂量表格等对不同照射角度及对应的照射时间在三维体素假体组织模型模拟计算得出的等效剂量分布进行评估，优选出可实施且符合需求的治疗计划方案。
第一实施例中硼中子捕获治疗系统的治疗计划模块30基于标准摄取值对感兴趣区域进行分组并通过计算给每一体素单元赋予相应的硼浓度数据，再结合医学影像数据及射束参数进行剂量模拟以制定治疗计划，使得硼原子在感兴趣区域内的分布更加符合实际情况，能够提高模型建立及剂量计算的精确性，确保了治疗计划的准确度，从而保证了治疗效果。可以理解，由于含硼药物费用昂贵，一般被照射体只在实际治疗时注射一次含硼药物，因此，在其他的可选的实施方式中，治疗计划制定时，硼浓度信息为预设，基于预设的硼浓度信息进一步生成治疗计划。
本发明第二实施例提供一硼中子捕获治疗系统，包括，中子照射装置10、治疗计划模块30以及控制模块40。中子照射装置10用于产生中子束并照射被照射体。治疗计划模块30用于基于感兴趣区域至少确定高浓度药物吸收区域、低浓度药物吸收区域，对高浓度药物区域和低浓度药物区域进行药物浓度赋值和剂量分布评估，生成治疗计划。控制模块40用于控制中子照射装置10执行治疗计划。其中，治疗计划模块30包括建模模块、处理模块、剂量评估模块以及治疗计划生成模块。建模模块、处理模块、剂量评估模块以及治疗计划生成模块依次电连接，并能够通过电连接进行数据的传输。
建模模块用于基于医学影像数据建立三维体素组织模型。可以理解的是，硼中子捕获治疗系统还包括影像装置，影像装置用于获取治疗计划模块30所需的医学影像数据。
医学影像数据为第一影像数据和第二影像数据的融合影像数据。具体的，第一影像数据为能够显示被照射体组织轮廓的影像数据。第二影像数据为能够显示出被照射体内摄取的药物分布的影像数据。其中，第二影像数据尤其为放射性核素医学影像数据，被照射体服用或注射的药物含有放射性标记物，以使药物在第二影像数据中显示出在被照射体内的分布情况，第二影像数据则包含能够描述标记物分布的标记物参数。
传统中子捕获治疗中，采用对病灶区域进行单一硼浓度赋值的方式，对于感兴趣区域的划分准确性要求较高，且依照不同医学影像所划分感兴趣区域具有差别，这种差别会导致剂量计算的不准确。若采用单一硼浓度赋值的方式，同时通过单一影像数据进行感兴趣区域划分，则会使计算结果更加不准确。比如，根据第一影像数据划分病灶区域，根据第二影像数据划分出药物摄取高的靶区。当病灶区域大于靶区时，表示病灶区域内有部分范围没有明显摄取到相应的药物，病灶区域小于靶区时，表示正常区域内摄取过多的药物，上述两种情况都会导致剂量计算出现偏差。即使当病灶区域与靶区接近时，两个区域内也会因为药物浓度 分布均匀性差等问题，使得剂量评估的最大剂量和最小剂量失真。
因此，第二实施例利用融合影像对感兴趣区域进行划分，避免了不同影像数据相应的缺陷，能够根据清晰的组织轮廓和摄取的药物分布划分出感兴趣区域，提高了划分感兴趣区域的准确性。同时，结合上述的将感兴趣区域划分为高浓度药物吸收区和低浓度药物吸收区，即改善了感兴趣区域划分的准确性对剂量计算的影响，又避免了传统的单一硼浓度赋值导致的剂量计算不准确的问题，进一步提高了剂量评估的准确性。
在一些实施例中，第一影像数据通过第一影像装置获取。第一影像装置为计算机断层扫描(Computed Tomography,CT)装置或核磁共振(Magnetic Resonance,MR)装置，具体可以为普通CT、增强CT、CTsim或MR。其中，CT对于骨胳的成像效果更好，MR对于软组织的成像效果更好。本实施例中，第一影像装置尤其可以采用CTsim，相比于其他影像获取装置，通过CTsim得到的影像具有更高的清晰度，能够提高后续步骤中的影像对位和区域划分的精确度，如图9所示，图9示出了根据CTsim影像划出的初步的病灶区域。第一影像数据不能显示药物分布的信息数据，在获取第一影像数据时，被照射体既可以服用或被注射含有标记物的药物，也可以未服用或未被注射含有标记物的药物。
在一些实施例中，第二影像数据通过第二影像装置获取，第二影像装置尤其为放射性核素医学影像获取设备。第二影像装置为多模式影像装置，多模式影像装置至少包括第一模式单元和第二模式单元。第一模式单元能够获取包含标记物参数的影像数据的第二功能影像，第二模式单元能够获得第二断面影像。第一模式单元和第二模式单元中的一个能够获取或生成第二功能影像和第二断面影像的变换矩阵，该变换矩阵可以实现第二功能影像和第二断面影像的配准融合。进一步的，利用变换矩阵将相同或不同成像方式的图像经过变换处理，使它们的空间位置和空间坐标达到匹配，利用各自成像方式的特点对两种图像进行空间配准，并将配准后的影像数据融合成为一个单一的影像。
进一步的，多模式影像装置具体可以为发射型计算机断层成像技术(Emission Computed Tomography，ECT)装置和其他影像装置的组合装置，例如：正电子发射断层(positron emission tomography，PET)装置与CT结合的PET-CT；单光子发射计算机断层成像术(Single-Photon Emission Computed Tomography，SPECT)与CT结合的SPECT-CT；或者正电子发射断层装置与核磁共振装置结合的PET-MR等。
在一些实施例中，第二影像装置也可以与第一影像装置为同一影像装置，该影像装置为多模式影像装置，例如：PET-CT、SPECT-CT或者PET-MR等，技术人员可以从该多模式影像装置所输出的影像数据中获得第一影像数据和第二影像数据所需的数据资料。
建模模块根据上述第一影像数据或融合影像数据进行三维体素组织建模，可以建立包含 标记物参数的三维体素组织模型，模型中的每一个体素单元具有相对应的药物分布参数和标记物参数。
处理模块，用于基于三维体素组织模型定义感兴趣区域。基于感兴趣区域至少确定高浓度药物吸收区域和低浓度药物吸收区域，将高浓度药物吸收区域和低浓度药物吸收区域进行分组。其中，高浓度药物吸收区域至少分为一组，低浓度药物吸收区域至少分为两组，每组进行药物浓度赋值。
处理模块可以根据上述的融合影像数据划出感兴趣区域，该感兴趣区域包含病灶的需要进行照射治疗的区域。根据第二影像数据所具备的标记物参数，结合第一影像数据所具备的清晰的被照射体内的组织轮廓，处理模块利用融合影像数据可以准确地、自动地划分出所需的感兴趣区域，如图10所示，图10示出了CTsim影像与PET影像融合后的融合影像，图10中红线圈定的范围为划定的感兴趣区域。在一些实施例中，操作人员可以操作处理模块12进行感兴趣区域的划分。
高浓度药物吸收区域和低浓度药物吸收区域之间的划分依据为表征药物浓度的某一指定值，该指定值通常以治疗效益为考量进行确定。
对于高浓度药物吸收区域，由于该区域的组织对药物的摄取率更高，从而形成了较高浓度的药物分布。高浓度药物吸收区域内的体素单元的药物浓度均大于上述指定值所表征的药物浓度，高浓度药物吸收区域的药物浓度分布均匀度高，对该区域进行均匀药物浓度赋值并进行剂量计算的结果与实际接受剂量吻合度较高，因此高浓度药物吸收区域可以至少划分一组。
对于低浓度药物吸收区域，由于该区域的组织对药物的摄取率更低，从而形成了较低浓度的药物分布。低浓度药物吸收区域内的体素单元的药物浓度均小于上述指定值所表征的药物浓度，低浓度药物吸收区域的药物浓度分布范围广，均匀性差，直接对该区域进行整体均匀药物浓度赋值并进行剂量计算的结果与实际接受剂量相差较大，因此需要对低浓度药物吸收区域划分为更多组，以进行非均匀药物浓度剂量计算，提高剂量评估的准确度与可信度，低浓度药物吸收区域可以至少划分两组。进一步的，高浓度药物吸收区域划分的组数小于低浓度药物吸收区域所划分的组数。
在一些实施例中，治疗计划模块30还用于定义TBR为感兴趣区域的药物浓度与血液中药物浓度的比值，定义TNR为感兴趣区域的药物浓度与正常组织中药物浓度的比值。处理模块根据TBR或TNR的值划分高浓度药物吸收区域和低浓度药物吸收区域，并根据TBR或TNR的值分别对高浓度药物吸收区域和低浓度药物吸收区域进行分组，TBR或TNR的值作为上述的指定值。
进一步的，处理模块确定感兴趣区域内TBR大于或等于第一指定值的区域为高浓度药物吸收区域，或确定TNR大于或等于第二指定值的区域为高浓度药物吸收区域。处理模块确定感兴趣区域的TBR小于第一指定值的区域或TNR小于第二指定值的区域为低浓度药物吸收区域。
在一些实施例中，被照射体服用或被注射的药物为硼药，当正常组织摄取硼药浓度低于血液硼浓度，即对于同一感兴趣区域的TNR大于TBR，第一指定值大于或等于1.2，第二指定值大于或等于1.5。
在一些实施例中，被照射体服用或被注射的药物为BPA，具体为18F-BPA，人体对于BPA的摄取情况为正常组织摄取硼浓度与血液硼浓度相近，即对于同一感兴趣区域的TNR等于TBR，第一指定值等于2.5，第二指定值等于2.5。
可以理解的是，TBR具有第N指定值，TNR具有第M指定值，第N指定值和第M指定值将感兴趣区域分成N+1或M+1个区域，其中，N和M为大于或等于1的整数。划分区域的总个数、高浓度药物吸收区域所划分区域的个数以及低浓度药物吸收区域所划分区域的个数均可以由药物种类、药物浓度分布均匀度、治疗的肿瘤类型以及被照射体的个体差异等因素进行确定。第N指定值和第M指定值的具体取值与指定值的种类(TBR还是TNR)、感兴趣区域的最大指定值和最小指定值、药物种类、治疗的肿瘤类型以及被照射体的个体差异等因素进行确定。
第二实施例中，处理模块用于将感兴趣区域分为三组，其中，将高浓度药物吸收区域分为一组，为第一区。将低浓度药物吸收区域分为两组，分别是第二区和第三区。其中，低浓度药物吸收区域的TBR大于或等于第三指定值或TNR大于或等于第四指定值的区域为第二区，低浓度药物吸收区域的TBR小于第三指定值或TNR小于第四指定值的区域为第三区。第三指定值大于1.5且小于等于2.0，第四指定值与第三指定值相等。进一步的，当药物为BPA时，第三指定值与第四指定值相等，且等于2.0。可以理解的是，上述的第一指定值、第二指定值、第三指定值和第四指定值均为TBR或TNR的取值。
给被照射体注射标记物标记药物并获取第二影像数据即可观测和获得药物摄取分布情况，由于标记物不影响药物本身药物动力学，因此利用含放射性核素标记物的药物分布情况具相当可信度。
本申请所记载实施例是基于放射性核素医学影像，如PET影像，来获取TBR或TNR，进而对感兴趣区域进行分组，因此被照射体注射药物为放射性核素标记药物。在其他实施例中，TBR或TNR的获取可以不通过医学影像获得，可抽血或提取组织进行药物浓度的测量，这种情况下注射药物可以是非放射性核素标记的普通药物。
治疗计划模块30还用于将药物浓度转化为基于医学影像数据获取的标记物放射性活度、标记物放射性强度、单位时间内衰变的原子数、互毁光子的有效计数以及标准摄取值中的一个数值进行定量或半定量分析，并得到相应的标记物的定量或半定量参数，记为标记物参数，上述的指定值为该标记物参数。在一些实施例中，影像装置可以直接将从第二影像数据或融合影像数据中获取标记物参数。作为优选的，放射性核素标记物可以为18F。
基于第二影像数据，本实施例中为PET影像，可获取各区域的标准摄取值SUV，TBR和TNR可分别由以下的式(1)和式(2)计算：

其中，SUVi为感兴趣区域第i个体素单元的SUV值，SUVblood为血液中的SUV值，SUVnormal为正常组织的SUV值。
处理模块对划分好的每组区域分别进行药物浓度赋值，在一些实施例中，对每组区域采用均匀药物浓度赋值方式。具体的，基于第V个区域的肿瘤体积对该区域的每个体素单元的TBR或TNR进行平均化计算，计算结果作为平均指定值。基于平均指定值获得该区域的均匀药物浓度，作为剂量分布评估的基础。
进一步的，药物为放射性核素标记的硼药，治疗计划模块30用于将硼浓度NB10转化为标准摄取值(StandardizedUptake Value，SUV)进行定量分析，如下公式六所示：
其中，NB10(V)表示第V个区域的10B原子的数量，即硼浓度，ξ为常数转换因子，为感兴趣区域中第V个区域的SUV平均值。感兴趣区域根据上述的方式被划分为V个区域，V＝1,2,3……。进一步的，处理模块可根据SUV值与硼浓度之间的转换关系自动定义或手动定义于三维体素组织模型中每一体素单元的硼浓度，基于硼浓度可计算获得每一体素内的硼的物理剂量。
在一些实施例中，剂量评估模块基于药物浓度和中子束的照射参数进行剂量评估。治疗计划生成模块基于剂量评估的结果生成治疗计划。
剂量评估模块通过内部预设的蒙特卡罗模拟程序模拟BNCT中患者被中子束照射时内部三维空间核粒子碰撞轨迹和能量分布，即可以模拟出物理剂量率分布，根据物理剂量率分布计算等效剂量率分布。在蒙特卡罗模拟程序中定义中子束的照射参数(如射束能量、强度、半径等)，模拟三维体素组织模型中每一体素单元在所定义的照射参数下单位时间所受到的 物理剂量。BNCT治疗的剂量计算中，造成剂量贡献的主要因子有硼剂量、中子剂量等，为能更直观的评估BNCT剂量，需要将剂量组成给予不同加权因素进行剂量评估，例如RBE和CBE等加权因素，以求得生物等效剂量(biologically equivalent dose)，如下公式七所示：
BNCTdose＝DB·CBE+Dn·RBEn+Dγ·RBEγ       (公式七)
其中，BNCTdose为中子照射下总的等效剂量，DB为硼的物理剂量，CBE为含硼药物的单位浓度的化合物生物效应，Dn为中子的物理剂量，RBEn为中子的相对生物效应，Dγ为光子的物理剂量，RBEγ为光子的相对生物效应。在一些实施例中，感兴趣区域的剂量可以代入CBE＝3.8，RBEn＝3.2，RBEγ＝1.0进行计算与评估。
在一些实施例中，可以通过剂量体积直方图(Dose Volume Histogram,DVH)、等剂量曲线、剂量表格等数学算法对三维体素组织模型模拟计算得出的等效剂量分布进行评估。
如图8所示，图8示出了本申请第二实施例硼中子捕获治疗系统的剂量评估方法的流程示意图，剂量评估方法包括以下步骤：
建模：基于被照射体的医学影像数据建立三维体素组织模型。具体的，基于医学影像数据建立三维体素组织模型的步骤还包括：获取第一影像数据；基于第一影像数据建立三维体素组织模型。进一步的，第一影像数据为能够显示被照射体组织轮廓的影像数据。
划定感兴趣区域：基于三维体素组织模型定义感兴趣区域。具体的，基于三维体素组织模型定义感兴趣区域的步骤还包括：获取第一影像数据；获取第二影像数据；将第一影像数据与第二影像数据进行配准对位，获得融合影像数据；基于融合影像数据划定感兴趣区域。其中，第一影像数据为CT或MRI，第二影像数据为放射性核素医学影像数据。
可以理解的，基于第一影像数据建立三维体素组织模型的步骤和获取第二影像数据、得到融合影像数据的步骤顺序不分先后。可以理解的，也可以基于融合影像数据建立三维体素组织模型。
分区分组：基于感兴趣区域至少确定高浓度药物吸收区域和低浓度药物吸收区域，将高浓度药物吸收区域和低浓度药物吸收区域进行分组，其中，高浓度药物吸收区域至少分为一组，低浓度药物吸收区域至少分为两组，每组进行药物浓度赋值。
具体的，分区分组的步骤还包括以下步骤：
以TBR或TNR进行分区：定义TBR为感兴趣区域的药物浓度与血液中药物浓度的比值，定义TNR为感兴趣区域的药物浓度与正常组织中药物浓度的比值；确定感兴趣区域的TBR大于或等于第一指定值的区域或TNR大于或等于第二指定值的区域为高浓度药物吸收区域，确定感兴趣区域的TBR小于第一指定值的区域或TNR小于第二指定值的区域为低浓度药物吸收区域。
根据药物确定指定值取值：药物为硼药，第一指定值大于或等于1.2，第二指定值大于或等于1.5；药物为BPA，第一指定值与第二指定值相等，为2.5。进一步的，药物为BPA时，以TBR或TNR进行分区的步骤还包括：将感兴趣区域分成三组，其中，将高浓度药物吸收区域分为一组，为第一区；将低浓度药物吸收区域分为两组，分别是第二区和第三区，低浓度药物吸收区域的TBR大于或等于第三指定值或TNR大于或等于第四指定值的区域为第二区，低浓度药物吸收区域的TBR小于第三指定值或TNR小于第四指定值的区域为第三区，第三指定值与第四指定值相等，等于2.0。
在一些实施例中，被照射体为脑瘤患者，该病患的肿瘤体积GTVanatomy范围较大，感兴趣区域的体积为155.9c.c.，即GTVanatomy为155.9c.c.。对该病患注射硼药18F-BPA，并从影像数据中获得TBR范围为0.70-5.95，如图11所示，则取第一指定值为2.5，将TBR≥2.5的区域划分为高浓度药物吸收区域并作为第一区，图11中绿色线条圈定的红色区域为第一区；将TBR＜2.5的区域划分为低浓度药物吸收区域。取第三指定值为2.0，将低浓度药物吸收区域划分为2.0≤TBR＜2.5的第二区和TBR＜2.0的第三区，图11中黄色线条圈定的橙色区域为第二区，红色线条圈定的绿色区域为第三区。
药物浓度赋值：基于第V个区域的肿瘤体积GTVanatomy对该区域的每个体素单元的TBR或TNR进行平均化计算，获取该区域的均匀硼浓度。
在上述病患的实施例中，划分出的第一区内的肿瘤体积GTV1为60.8c.c.，基于图12所示的TBR-体积直方图计算该区域内的平均指定值(即平均TBR)为3.30，第二区内的肿瘤体积GTV2为63.0c.c.，基于图12计算该区域内的平均TBR为2.26，第三区的肿瘤体积GTV3为35.1c.c.，基于图12计算该区域内的平均TBR为1.67。采用均匀硼浓度分布赋值，上述每一平均TBR对应于一个硼浓度值。
剂量评估：基于药物浓度和中子束的照射参数进行剂量评估。
具体的，剂量评估的步骤包括：基于药物浓度和中子束的照射参数计算照射剂量。
针对上述病患，利用现有治疗计划系统NeuMANTA计算非均匀硼浓度分布剂量功能的结果为对照计算组，并与第二实施例所提供的剂量评估结果进行比较。对照组的计算中，将GTVanatomy所有硼浓度进行132区域群化，并对132个区域进行硼浓度赋值，相当于将GTVanatomy区分为132个区域进行均匀硼浓度分布剂量计算。本第二实施例中，将GTVanatomy区分为3个区域进行均匀硼浓度分布剂量计算。
第二实施例的剂量计算时间相比于对照组计算时间缩短近80％，这是在对照组的计算中，由于132个区域中部分区域之间的硼浓度差异较小，硼浓度的赋值差别对剂量计算的影响微乎其微，反而增加了计算的时间，且占用了较高的内存。本申请第二实施例的分区分组方式， 在确保剂量结果具有高可信度和高准确度的情况下，极大程度降低了剂量计算的时间，并进而降低了治疗计划制定所用时间，也降低了治疗计划系统10对于硬件设备的要求和依赖，提高了治疗过程的便捷性。本申请第二实施例和对照组的GTVanatomy剂量结果与差异如图13和下表所示：
其中，Dmax为被照射体模拟治疗计算中获得最大剂量，Dmin为被照射体模拟治疗计算中获得最小剂量，Dmean为被照射体模拟治疗计算中获得平均剂量，D80为病灶80％体积获得的剂量，单位为Gy-Eq；图13中，实线表示本申请第二实施例的方法的剂量体积直方图，虚线表示对照组方法的剂量体积直方图，横坐标Dose(Gy-Eq)为照射剂量，纵坐标Volume(％)为病灶体积百分比。
从上表和图13中可以看出，两种方式的DVH分布具有相当的一致性。具体的，按照本申请第二实施例的方式计算的结果在Dmin、Dmean以及D80时与非均匀硼浓度的计算结果的偏差不超过15％，尤其在Dmean以及D80时，均匀硼浓度的计算结果与非均匀硼浓度的计算结果之间的偏差不超过5％。由于在实际治疗中，为了能给予病灶良好的控制，实际治疗的剂量常以低剂量为参考依据，如采用病灶80％体积获得的剂量D80为参考依据，从而确保病灶能够获得足够处方剂量的同时降低对病患身体健康的影响。由上可知，以D80为评估标准，本申请实施例的计算结果相比于对照的非均匀硼浓度的计算结果偏差较小，所以，本申请方法在节省计算时间的同时，能够保证剂量计算的准确性。
可以理解的，上述剂量评估方法可以在硼中子捕获治疗系统中应用执行。
应该理解的是，虽然如上所述的各实施例所涉及的流程图中的各个步骤按照箭头的指示依次显示，但是这些步骤并不是必然按照箭头指示的顺序依次执行。除非本文中有明确的说明，这些步骤的执行并没有严格的顺序限制，这些步骤可以以其它的顺序执行。而且，如上所述的各实施例所涉及的流程图中的至少一部分步骤可以包括多个步骤或者多个阶段，这些步骤或者阶段并不必然是在同一时刻执行完成，而是可以在不同的时刻执行，这些步骤或者阶段的执行顺序也不必然是依次进行，而是可以与其它步骤或者其它步骤中的步骤或者阶段的至少一部分轮流或者交替地执行。
以上实施例的各技术特征可以进行任意的组合，为使描述简洁，未对上述实施例中的各个技术特征所有可能的组合都进行描述，然而，只要这些技术特征的组合不存在矛盾，都应 当认为是本说明书记载的范围。以上所述实施例仅表达了本申请的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对本申请专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本申请构思的前提下，还可以做出若干变形和改进，这些都属于本申请的保护范围。因此，本申请的保护范围应以所附权利要求为准。

Claims (27)

  1. 一种硼中子捕获治疗系统，其特征在于，包括：
    中子束照射装置，用于产生中子束并照射被照射体；
    治疗计划模块，用于对三维体素假体组织模型中的每一体素单元进行硼浓度赋值并生成治疗计划；及
    控制模块，用于根据所述治疗计划控制所述中子束照射装置执行照射。
  2. 根据权利要求1所述的硼中子捕获治疗系统，其特征在于，所述治疗计划模块基于标准摄取值对三维体素假体组织模型中的感兴趣区域进行分组并计算每一组的标准摄取值的平均值。
  3. 根据权利要求2所述的硼中子捕获治疗系统，其特征在于，每一组标准摄取值SUV的平均值采用公式二进行计算：
    其中，I为组数，本发明一实施例中设为偶数、SUVROI,upper为感兴趣区域内的SUV值的上限值、SUVROI,lower为感兴趣区域内的SUV值的下限值。
  4. 根据权利要求3所述的硼中子捕获治疗系统，其特征在于，所述组数I大于等于10小于等于500。
  5. 根据权利要求3所述的硼中子捕获治疗系统，其特征在于，所述组数I大于等于10小于等于100。
  6. 根据权利要求3所述的硼中子捕获治疗系统，其特征在于，所述组数I等于40、44、50、54或60。
  7. 根据权利要求3所述的硼中子捕获治疗系统，其特征在于，所述治疗计划模块基于归一化因子k调整组数I或者SUV平均值，归一化因子k采用公式三进行计算：
    其中，SUVROI(V)为感兴趣区域内中第V个体素SUV值、∫VSUVROI(V)dV为未分组前SUV总值、Ni为第i组的计数、k为归一化因子、为分组后SUV总值。
  8. 根据权利要求7所述的硼中子捕获治疗系统，其特征在于，所述治疗计划模块根据公式四确定感兴趣区域中每一体素内的硼浓度NB10,group(V)，公式四如下：
    其中，ξ为常数转换因子，其用于将SUV值转换为相应的10B原子数量、i表示组群索引、SUVROI(V)为感兴趣区域中第V个体素SUV值。
  9. 根据权利要求1所述的硼中子捕获治疗系统，其特征在于，所述治疗计划模块，用于基于所述被照射体的感兴趣区域至少确定高浓度药物吸收区域和低浓度药物吸收区域，并对所述高浓度药物吸收区域和所述低浓度药物吸收区域进行药物浓度赋值和剂量评估，生成治疗计划。
  10. 根据权利要求9所述的硼中子捕获治疗系统，其特征在于，所述治疗计划模块包括：
    建模模块，用于基于所述被照射体的医学影像数据建立三维体素组织模型；
    处理模块，用于基于所述三维体素组织模型定义感兴趣区域，基于所述感兴趣区域至少确定高浓度药物吸收区域和低浓度药物吸收区域，将所述高浓度药物吸收区域和所述低浓度药物吸收区域进行分组，其中，所述高浓度药物吸收区域至少分为一组，所述低浓度药物吸收区域至少分为两组，每组进行药物浓度赋值；
    剂量评估模块，基于所述药物浓度和所述中子束的照射参数进行剂量评估；
    治疗计划生成模块，基于所述剂量评估的结果生成治疗计划。
  11. 根据权利要求10所述的硼中子捕获治疗系统，其特征在于，所述治疗计划模块，还用于定义TBR为所述感兴趣区域的药物浓度与血液中药物浓度的比值，定义TNR为所述感兴趣区域的药物浓度与正常组织中药物浓度的比值；
    所述处理模块，用于确定所述感兴趣区域的TBR大于或等于第一指定值的区域或TNR大于或等于第二指定值的区域为所述高浓度药物吸收区域，确定所述感兴趣区域的TBR小于所述第一指定值的区域或TNR小于所述第二指定值的区域为所述低浓度药物吸收区域。
  12. 根据权利要求11所述的硼中子捕获治疗系统，其特征在于，所述药物为硼药，所述第一指定值大于或等于1.2，所述第二指定值大于或等于1.5。
  13. 根据权利要求12所述的硼中子捕获治疗系统，其特征在于，所述药物为BPA，所述第一指定值等于2.5，所述第二指定值等于2.5。
  14. 根据权利要求13所述的硼中子捕获治疗系统，其特征在于，所述处理模块，用于将所述感兴趣区域分为三组，其中，将所述高浓度药物吸收区域分为一组，为第一区；将所述低浓度药物吸收区域分为两组，分别是第二区和第三区，其中，所述低浓度药物吸收区域的TBR大于或等于第三指定值或TNR大于或等于第四指定值的区域为第二区，所述低浓度药 物吸收区域的TBR小于第三指定值或TNR小于第四指定值的区域为第三区，所述第三指定值大于1.5且小于等于2.0，所述第四指定值与第三指定值相等。
  15. 根据权利要求14所述的硼中子捕获治疗系统，其特征在于，所述第四指定值等于所述第三指定值，等于2.0。
  16. 根据权利要求12所述的硼中子捕获治疗系统，其特征在于，所述药物为放射性核素标记的硼药，所述治疗计划模块，还用于将所述药物浓度转化为基于医学影像数据获取的标记物放射性活度、标记物放射性强度、单位时间内衰变的原子数、互毁光子的有效计数以及标准摄取值中的一个数值进行定量或半定量分析。
  17. 根据权利要求16所述的硼中子捕获治疗系统，其特征在于，所述治疗计划模块，用于将所述药物浓度转化为标准摄取值SUV进行定量分析，
    其中，NB10(V)表示第V个区域的10B原子的数量，ξ为常数转换因子，为感兴趣区域中第V个区域的SUV平均值。
  18. 一种硼中子捕获治疗系统的治疗计划生成方法，其特征在于，包括以下步骤：
    建立带有组织种类、组织密度数据的三维体素假体组织模型；
    对三维体素假体组织模型中的每一体素单元进行硼浓度赋值；
    基于硼浓度赋值和中子束的照射参数进行剂量评估，获取剂量分布。
    根据计算结果对照射角度进行优选生成治疗计划。
  19. 根据权利要求18所述的治疗计划生成方法，其特征在于，所述建立带有组织种类、组织密度数据的三维体素假体组织模型的步骤包括：
    读取医学影像数据；
    建立三维医学影像体素模型；
    定义感兴趣区域的边界；
    定义每一体素单元的组织种类(元素组成)、组织密度。
  20. 根据权利要求19所述的治疗计划生成方法，其特征在于，所述对三维体素假体组织模型中的每一体素单元进行硼浓度赋值的步骤包括：
    基于标准摄取值对感兴趣区域进行分组；
    确定感兴趣区域中每一体素内的硼浓度。
  21. 根据权利要求20所述的治疗计划生成方法，其特征在于，所述对感兴趣区域进行分组的步骤包括：通过公式一将影像中感兴趣区域内每一体素中的10B信息可转换为SUV值的 步骤，公式一如下：
    其中，ROI为在影像中定义的感兴趣区域、Acitivity Concentration in ROI为感兴趣区域内每单位体积的平均放射性活度、Injected Dose为注射的放射性活度、body weight为被照射体的体重。
  22. 根据权利要求18所述的治疗计划生成方法，其特征在于，所述剂量评估的方法包括：
    基于被照射体的医学影像数据建立三维体素组织模型；
    基于所述三维体素组织模型定义感兴趣区域；
    基于所述感兴趣区域至少确定高浓度药物吸收区域和低浓度药物吸收区域，将所述高浓度药物吸收区域和所述低浓度药物吸收区域进行分组，其中，所述高浓度药物吸收区域至少分为一组，所述低浓度药物吸收区域至少分为两组，每组进行药物浓度赋值；
    基于所述药物浓度和中子束的照射参数进行剂量评估。
  23. 根据权利要求22所述的治疗计划生成方法，其特征在于，所述基于所述感兴趣区域至少确定高浓度药物吸收区域和低浓度药物吸收区域的步骤包括：定义TBR为所述感兴趣区域的药物浓度与血液中药物浓度的比值，定义TNR为所述感兴趣区域的药物浓度与正常组织中药物浓度的比值；确定所述感兴趣区域的TBR大于或等于第一指定值的区域或TNR大于或等于第二指定值的区域为所述高浓度药物吸收区域，确定所述感兴趣区域的TBR小于第一指定值的区域或TNR小于第二指定值的区域为所述低浓度药物吸收区域。
  24. 根据权利要求23所述的治疗计划生成方法，其特征在于，所述药物为硼药，所述第一指定值大于或等于1.2，所述第二指定值大于或等于1.5。
  25. 根据权利要求24所述的治疗计划生成方法，其特征在于，所述药物为BPA，所述第一指定值与第二指定值相等，为2.5。
  26. 根据权利要求25所述的治疗计划生成方法，其特征在于，将感兴趣区域分成三组，其中，将所述高浓度药物吸收区域分为一组，为第一区；将所述低浓度药物吸收区域分为两组，分别是第二区和第三区，所述低浓度药物吸收区域的TBR大于或等于第三指定值或TNR大于或等于第四指定值的区域为第二区，所述低浓度药物吸收区域的TBR小于第三指定值或TNR小于第四指定值的区域为第三区，所述第三指定值与第四指定值相等，所述第三指定值大于1.5且小于等于2.0。
  27. 根据权利要求26所述的治疗计划生成方法，其特征在于，所述药物为放射性核素标记的硼药，将所述药物浓度转化为标准摄取值SUV进行定量分析，
    其中，NB10(V)表示第V个区域的10B原子的数量，ξ为常数转换因子，为感兴趣区域中第V个区域的SUV平均值。
PCT/CN2023/129862 2022-11-07 2023-11-06 硼中子捕获治疗系统及其治疗计划生成方法 WO2024099252A1 (zh)

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