Boron neutron capture therapy system and treatment plan generation method

Abstract

The present application relates to a boron neutron capture therapy system (100) and a method of operating the same, the boron neutron capture therapy system (100) including a neutron beam irradiation device (10), a treatment planning module (30), and a control module (40), wherein the neutron beam irradiation device (10) generates a neutron beam and irradiates the neutron beam to an irradiated body, the treatment planning module (30) sets a boron concentration for each voxel unit in a three-dimensional voxel prosthetic tissue model to generate a treatment plan, and the control module (40) controls the neutron beam irradiation device (10) to irradiate based on the treatment plan. The treatment planning module (30) sets corresponding boron concentration data for each voxel unit, and then combines it with medical image data to perform dose simulation to formulate a treatment plan, thereby making the distribution of boron atoms in the region of interest more consistent with the actual situation, improving the accuracy of model establishment and dose calculation, and ensuring the accuracy of the treatment plan, thereby guaranteeing the treatment effect.

Description

[Technical Field]

[0001] The present application relates to the technical field of radiation therapy, and more particularly to a boron neutron capture therapy system and a treatment plan generation method therefor. [Background technology]

[0002] With the development of atomic science, radiation therapy using cobalt-60, linear accelerators, electron beams, etc. has become one of the main means of cancer treatment. However, conventional photon or electron therapy kills tumor cells due to the limitations of the physical conditions of the radiation itself, while damaging many normal tissues along the beam path. In addition, tumor cells have different degrees of sensitivity to radiation, so conventional radiation therapy is not very effective in treating malignant tumors with high radiation resistance (e.g., glioblastoma multiforme, melanoma).

[0003] To reduce radiation damage to normal tissues surrounding tumors, the concept of targeted therapy in chemotherapy has been applied to radiotherapy, and for tumor cells with high radiation resistance, radiotherapy with high relative biological effectiveness (RBE), such as proton therapy, heavy ion therapy, and neutron capture therapy, is currently being actively developed. Among these, boron neutron capture therapy, a type of neutron capture therapy, provides a better cancer treatment option than conventional radiotherapy by specifically collecting boron-containing drugs in tumor cells, which, combined with highly precise neutron beam control, provides a better cancer treatment option than conventional radiotherapy.

[0004] In boron neutron capture therapy (BNCT), boron ( 10 B) Taking advantage of the property that the contained drug has a large capture cross section for thermal neutrons, 10 B(n,α) 7 Li neutron capture and fission reactions 4 He and 7Two types of heavy charged particles, Li, are generated. The two types of heavy charged particles have an average energy of approximately 2.33 MeV, a high linear energy transfer (LET), and a short range. The linear energy transfer and range of the alpha particles are 150 keV / μm and 8 μm, respectively. 7 In the case of Li heavy charged particles, the energy is 175 keV / μm and 5 μm, and the total range of the two types of particles is approximately the size of a single cell, so that radiation damage to the living body is limited to the cellular level, and boron-containing drugs selectively accumulate in tumor cells. When combined with an appropriate neutron source, the goal of locally killing tumor cells can be achieved without causing significant damage to normal tissues.

[0005] During boron neutron capture therapy, the neutron beam used to irradiate the patient is intense. Therefore, precise control of the radiation dose administered to the patient is essential to achieve a high therapeutic effect while minimizing radiation damage to the patient. Therefore, the accuracy of treatment planning is crucial. To simulate the absorbed dose of the human body under specific radiation conditions and assist physicians in planning treatment, computer technology must be used to process medical image data in various ways to accurately establish the lattice model required for Monte Carlo software and then perform simulation calculations in combination with the software. In the field of neutron capture therapy, when establishing the lattice model required for Monte Carlo software based on medical image data for dose calculation and evaluation, basic biological information reflected by each lattice, such as tissue type and boron concentration, must be defined in the model. The reliability of dose calculation results depends on the accuracy and precision of the information. However, the boron concentration information is usually a regional boron concentration value given in the corresponding model region by obtaining the boron concentration data of the sample based on a blood sample test or a slice test and estimating the boron concentration of the corresponding tissue and tumor. The boron concentration information given in this way does not take into account the true distribution of the boron drug in the body and the metabolic status of the boron drug over time, which affects the reliability of the dose calculation results, reduces the accuracy of the treatment plan, and results in unsatisfactory treatment effects. Summary of the Invention [Problem to be solved by the invention]

[0006] Therefore, in order to address the above technical issues, it is necessary to provide a boron neutron capture therapy system and a method for generating a treatment plan therefor that can guarantee therapeutic effects. [Means for solving the problem]

[0007] A boron neutron capture therapy system according to one embodiment of the present invention includes a neutron beam irradiation device, a treatment planning module, and a control module, wherein the neutron beam irradiation device generates a neutron beam and irradiates the neutron beam onto a subject, the treatment planning module sets a boron concentration for each voxel unit in a three-dimensional voxel prosthetic tissue model to generate a treatment plan, and the control module controls the neutron beam irradiation device to irradiate based on the treatment plan.

[0008] Additionally, the treatment planning module groups regions of interest in the three-dimensional voxel prosthetic tissue model based on the normalized uptake values ​​and calculates the average normalized uptake value within the regions of interest in each group.

[0009] Additionally, the mean standardized uptake value SUV for each group is calculated using Equation 2.

number

[0010] Furthermore, the number of groups I is 10 or more and 500 or less.

[0011] Furthermore, the number of groups I is 10 or more and 100 or less.

[0012] Furthermore, the number of groups I is equal to 40, 44, 50, 54 or 60.

[0013] Additionally, the treatment planning module adjusts the number of groups I or the mean value of SUV based on a normalization factor k, which is calculated using Equation 3.

number

number

number

[0014] Furthermore, the treatment planning module calculates the boron concentration N in each voxel in the region of interest based on Equation 4. B10 , group(V) is determined, and Equation 4 is as follows:

number

[0015] A boron neutron capture therapy system according to a second aspect of the present invention includes a neutron irradiation device, a treatment planning module, and a control module, wherein the neutron irradiation device generates a neutron beam and irradiates the neutron beam onto an irradiated body, the treatment planning module determines 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, and performs drug concentration setting and dose evaluation for the high concentration drug absorption region and the low concentration drug absorption region to generate a treatment plan, and the control module controls the neutron irradiation device to execute the treatment plan.

[0016] Further, the treatment planning module includes a model establishment module, a processing module, a dose evaluation module, and a treatment plan generation module; the model establishment module establishes a three-dimensional voxel tissue model based on the medical image data of the irradiated object; the processing module defines a region of interest based on the three-dimensional voxel tissue model, determines at least a region of high drug absorption and a region of low drug absorption based on the region of interest, groups the regions of high drug absorption and the regions of low drug absorption such that the regions of high drug absorption are divided into at least one group and the regions of low drug absorption are divided into at least two groups, and sets a drug concentration for each group; the dose evaluation module performs dose evaluation based on the drug concentration and the irradiation parameters of the neutron beam; The treatment plan generation module generates a treatment plan based on results of the dose assessment.

[0017] Furthermore, the treatment planning module further defines a TBR as a ratio of a drug concentration in the region of interest to a drug concentration in blood, and a TNR as a ratio of a drug concentration in the region of interest to a drug concentration in normal tissue; The processing module determines areas of the region of interest where the TBR is greater than or equal to a first specified value or the TNR is greater than or equal to a second specified value as the high concentration drug absorption area, and determines areas of 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 the low concentration drug absorption area.

[0018] Furthermore, when the drug is a boron drug and the concentration of the boron drug taken up into normal tissue is lower than the blood boron concentration, i.e., when the TNR of the same region of interest is greater than the TBR, the first specified value is 1.2 or more and the second specified value is 1.5 or more.

[0019] Furthermore, when the drug is BPA and the uptake situation of BPA in the human body is such that the boron concentration incorporated into normal tissues is close to the boron concentration in blood, i.e., the TNR of the same region of interest is equal to the TBR, the first specified value is equal to 2.5 and the second specified value is equal to 2.5.

[0020] Additionally, the drug may be labeled with a radionuclide. 18 It is F-BPA.

[0021] Further, the processing module divides the region of interest into three groups, wherein the high concentration drug absorption region is divided into one group designated as the first region, and the low concentration drug absorption region is divided into two groups designated as the second and third regions, respectively, and the region in the low concentration drug absorption region where the TBR is greater than or equal to a third designated value or the TNR is greater than or equal to a fourth designated value is the second region, and the region in the low concentration drug absorption region where the TBR is smaller than the third designated value or the TNR is smaller than the fourth designated value is the third region, the third designated value being greater than 1.5 and less than or equal to 2.0, and the fourth designated value being equal to the third designated value.

[0022] Furthermore, the third specified value is equal to the fourth specified value, which is equal to 2.0.

[0023] Furthermore, the drug is a drug labeled with a radioactive nuclide, and the treatment planning system further converts the drug concentration into one of the following values: the radioactivity of the marker, the radioactivity intensity of the marker, the number of atoms decaying per unit time, the effective count of photons generated by annihilation, and the standardized uptake value, all of which are obtained based on medical image data, to perform quantitative or semi-quantitative analysis.

[0024] Furthermore, the drug is a radionuclide labeled boron drug, and the treatment planning system converts the drug concentration into a standardized uptake value (SUV) for quantitative analysis.

[0025]

number

number

[0026] A treatment plan generation method for a boron neutron capture therapy system according to a third aspect of the present invention includes the steps of establishing a three-dimensional voxel prosthetic tissue model having tissue type and tissue density data, setting boron concentration for each voxel unit in the three-dimensional voxel prosthetic tissue model, obtaining a dose distribution, and selecting a preferred irradiation angle based on the calculation results to generate a treatment plan.

[0027] Further, the step of establishing a three-dimensional voxel prosthesis tissue model having tissue type and tissue density data includes the steps of reading medical image data, establishing a three-dimensional medical image voxel model, defining the boundary of the region of interest, and defining the tissue type (elemental composition) and tissue density of each voxel unit.

[0028] Further, the step of setting a boron concentration for each voxel unit in the three-dimensional voxel prosthetic tissue model includes the steps of grouping regions of interest based on normalized uptake values ​​and determining the boron concentration in each voxel within the regions of interest.

[0029] Furthermore, the step of grouping the regions of interest may be performed by: 10 The step of converting the B information into an SUV value is shown in Equation 1 as follows:

number

[0030] Furthermore, the step of grouping the regions of interest is specifically a step of adjusting the number of groups I or the mean value of the SUV by a normalization coefficient k.

[0031] Furthermore, the normalization factor k is calculated using the following formula:

number

number

number

number

number

number

[0032] Furthermore, the boron concentration N B10 , group (V) is calculated using Equation 4.

number

[0033] A treatment plan generation method for a boron neutron capture therapy system according to a fourth aspect of the present invention includes the steps of: establishing a three-dimensional voxel tissue model based on medical image data of an irradiated body; defining a region of interest based on the three-dimensional voxel tissue model; determining at least high-concentration drug absorption regions and low-concentration drug absorption regions based on the region of interest, grouping the high-concentration drug absorption regions and the low-concentration drug absorption regions so that the high-concentration drug absorption regions are divided into at least one group and the low-concentration drug absorption regions are divided into at least two groups, and setting a drug concentration for each group; performing dose evaluation based on the drug concentrations and neutron beam irradiation parameters to obtain a dose distribution; and selecting a preferred irradiation angle based on the calculation results to generate a treatment plan.

[0034] Furthermore, 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 the steps of defining TBR as the ratio of the drug concentration in the region of interest to the drug concentration in 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 of the region of interest where the TBR is equal to or greater than a first specified value or where the TNR is equal to or greater than a second specified value as the high concentration drug absorption region, and determining a region of the region of interest where the TBR is smaller than the first specified value or where the TNR is smaller than the second specified value as the low concentration drug absorption region.

[0035] Furthermore, the drug is a boron drug, the first specified value is 1.2 or greater, and the second specified value is 1.5 or greater.

[0036] Furthermore, the drug is BPA, and the first specified value is equal to the second specified value, which is 2.5.

[0037] Additionally, the drug may be labeled with a radionuclide.18 It is F-BPA.

[0038] Further, the regions of interest are divided into three groups, wherein the high-concentration drug absorption region is divided into one group designated as the first region, and the low-concentration drug absorption region is divided into two groups designated as the second and third regions, and the regions of the low-concentration drug absorption region where the TBR is greater than or equal to a third designated value or the TNR is greater than or equal to a fourth designated value are the second regions, and the regions of the low-concentration drug absorption region where the TBR is smaller than the third designated value or the TNR is smaller than the fourth designated value are the third regions, and the third designated value is equal to the fourth designated value, and the third designated value is greater than 1.5 and less than or equal to 2.0.

[0039] Furthermore, the third specified value is equal to the fourth specified value, which is equal to 2.0.

[0040] Furthermore, the drug is a radionuclide-labeled boron drug, and the drug concentration is converted into a standardized uptake value (SUV) for quantitative analysis.

[0041]

number

number

[0042] Further, the step of defining the region of interest includes the steps of acquiring first image data of the irradiated object, acquiring second image data of the irradiated object, aligning the first image data and the second image data to acquire fused image data, and defining the region of interest based on the fused image data.

[0043] Furthermore, the first image data is CT or MRI, and the second image data is radionuclide medical image data. [Effects of the Invention]

[0044] The treatment planning module in the boron neutron capture therapy system according to the first and third aspects of the present invention sets corresponding boron concentration data for each voxel unit, and then combines it with medical image data to perform dose simulation to formulate a treatment plan, thereby making the distribution of boron atoms in the region of interest more consistent with the actual situation, improving the accuracy of model establishment and dose calculation, and ensuring the accuracy of the treatment plan, thereby guaranteeing the therapeutic effect.

[0045] The boron neutron capture therapy system and its dose evaluation method according to the second and fourth aspects of the present invention divide the region of interest into at least a high drug absorption region and a low drug absorption region, thereby avoiding the problem of excessive grouping resulting in an increase in the Monte Carlo simulation calculation time due to the large number of boron concentration values, and also avoiding the problem of insufficient calculation reliability due to setting a single boron concentration, and further optimizing the treatment plan by improving the accuracy and reliability of dose evaluation. The present application ensures the accuracy of dose calculation and ensures that the lesion range receives a sufficient prescribed dose, while significantly reducing the amount of Monte Carlo simulation calculation and shortening the calculation time, thereby enabling faster and more accurate generation of treatment plans and improving the operating efficiency of the therapy system. [Brief explanation of the drawings]

[0046] [Figure 1] FIG. 1 is a schematic diagram of a boron neutron capture reaction. [Figure 2] This is the nuclear reaction equation for neutron capture in 10B(n,α)7Li. [Figure 3] 1 is a block diagram of a neutron capture therapy system according to an embodiment of the present invention. [Figure 4]1 is a structural schematic diagram of a neutron irradiation device according to an embodiment of the present invention. [Figure 5] 1 is a flowchart of a treatment plan generation method in one embodiment of the present invention. [Figure 6] 1 is a flowchart of a method for establishing a three-dimensional voxel prosthetic tissue model in accordance with one embodiment of the present invention. [Figure 7] 1 is a flowchart of a method for providing boron concentration data for each voxel unit in a three-dimensional voxel prosthetic tissue model in accordance with one embodiment of the present invention. [Figure 8] 10 is a flowchart of a method for dose evaluation in boron neutron capture therapy in another embodiment of the present invention. [Figure 9] 10 is a schematic diagram of a CTsim image and a lesion region in another embodiment of the present invention; [Figure 10] FIG. 10 is a schematic diagram of a fused image and a region of interest in another embodiment of the present invention. [Figure 11] FIG. 10 is a schematic diagram of dividing a region of interest in another embodiment of the present invention; [Figure 12] 10 is a TBR volume histogram of a region of interest in accordance with another embodiment of the present invention; [Figure 13] FIG. 10 is a schematic diagram of a comparison with a dose-volume histogram of a control group in another embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0047] In order to clarify the purpose, technical means and advantages of the present application, the present application will be described in detail below with reference to the drawings and examples. Note that the specific examples described in this specification are only for the purpose of interpreting the present application and are not intended to limit the present application.

[0048] Preferably, a neutron capture therapy system and a treatment plan generation method therefor are embodiments of the present invention. Neutron capture therapy, and in particular boron neutron capture therapy, will be briefly described below.

[0049] In boron neutron capture therapy (BNCT), boron ( 10 B) Taking advantage of the property that the contained drug has a large capture cross section for thermal neutrons, 10 B(n,α) 7 Li neutron capture and fission reactions 4 He and 7 Figures 1 and 2 show a schematic diagram of the boron neutron capture reaction and the 10 B(n,α) 7 The nuclear reaction formula for Li neutron capture is shown in Figures 1 and 2. As shown in Figures 1 and 2, the two types of charged particles have the average energy of approximately 2.33 MeV, high linear energy transfer, and short range. The linear energy transfer and range of α particles are 150 keV / μm and 8 μm, respectively. 7 In the case of Li heavy charged particles, the energy is 175 keV / μm and 5 μm, and the total range of the two types of particles is approximately the size of a single cell, so that radiation damage to the living body is limited to the cellular level, and boron-containing drugs selectively accumulate in tumor cells. When combined with an appropriate neutron source, the goal of locally killing tumor cells can be achieved without causing significant damage to normal tissues.

[0050] The Monte Carlo method can accurately simulate the collision trajectories and energy distribution of nuclear particles in three-dimensional space within a radiation target. In boron neutron capture therapy, to simulate the absorbed dose in the human body under specific radiation conditions and help doctors formulate treatment plans, computer technology must be used to perform various processing on medical images to accurately establish the lattice model required for Monte Carlo software, and then combine it with the Monte Carlo software to perform simulation calculations and ultimately obtain a treatment plan. Medical image data can be magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), PET-CT, or X-ray imaging. As known to those skilled in the art, other medical image data can also be used. As long as the medical image data can be converted into a three-dimensional voxel prosthetic tissue model, it can be applied to the radiation therapy system and treatment plan generation method disclosed in the present invention.

[0051] As shown in FIG. 3, a boron neutron capture therapy system 100 according to an embodiment of the present invention includes a neutron beam irradiation device 10, an image acquisition module 20, a treatment planning module 30, and a control module 40. The neutron beam irradiation device 10 includes a neutron generator 11 and a treatment couch 12. The neutron generator 11 generates a therapeutic neutron beam N during radiation irradiation treatment and irradiates boron ( 10B) The treatment is performed by irradiating the irradiated subject into which the contained drug has been taken. Before treatment, the treatment planning module 30 generates a treatment plan based on information such as medical image data of the irradiated area of ​​the irradiated subject and parameters of the therapeutic neutron beam N generated by the neutron generator 11. During radiation irradiation treatment, the control module 40 retrieves the treatment plan corresponding to the current irradiated subject from the treatment planning module 30 and controls the neutron beam irradiator 10 to irradiate based on the treatment plan. In this embodiment, the parameters of the therapeutic neutron beam N used by the treatment planning module 30 to generate the treatment plan are a neutron beam model generated based on radiation source parameters.

[0052] As shown in FIG. 4 , the neutron irradiation device 100 includes a radiation generator 110 and a beam shaper 120. The radiation generator 110 includes an accelerator 111, a beam transport device 112, and a target T. The accelerator 111 accelerates charged particles (e.g., protons, deuterium nuclei, etc.) to generate a charged particle beam P such as a proton beam. The charged particle beam P is irradiated onto the target T and interacts with the target T to generate a neutron beam (neutron beam) N. The target T is preferably a metal target, and in the embodiment of the present invention, a target made of lithium metal is preferably used. However, as is well known to those skilled in the art, the target may be made of a metal material other than lithium or beryllium, such as tantalum (Ta) or tungsten (W). The target may be disk-shaped, have another solid shape, or be a liquid (liquid metal).

[0053] The end of the beam shaper 120 close to the irradiated object M has a collimator 126 that focuses the neutron beam. The beam shaper 120 adjusts the beam quality of the neutron beam, and the neutron beam N generated by the radiation generator 20 passes through the beam shaper 120 in order and is irradiated to the irradiated object M from a beam exit 127. By focusing the neutron beam, the neutron beam has high targetability during the treatment process. As can be understood, this embodiment does not have the collimator 126, and the beam may be directly irradiated to the irradiated object M after exiting the beam shaper 120.

[0054] The beam shaper 120 further includes a reflector 121, a moderator 122, a thermal neutron absorber 123, a radiation shield 124, and a beam passage 125. Since the neutrons generated by the radiation generator 110 have a wide energy spectrum, in order to avoid harm to the operator or the irradiated subject, it is necessary to reduce the content of other types of neutrons and photons as much as possible in addition to epithermal neutrons that meet the treatment needs. Therefore, it is necessary to pass the neutrons emitted from the target T through the moderator 2212 to convert the fast neutrons (energy: >10 keV) into epithermal neutrons (energy range: 0.5 eV to 10 keV) and reduce the thermal neutrons (<0.5 eV) as much as possible. The moderator 2212 is made of a material with a large cross section for fast neutrons and a small cross section for epithermal neutrons, preferably at least one of DO, AlF, Fluental (registered trademark), CaF, LiCO, MgF, and AlO. The reflector 121 surrounds the moderator 122 and reflects neutrons that pass through the moderator 122 and diffuse into the surrounding area back into the neutron beam N, thereby improving neutron utilization. The reflector 121 is made of a material with high neutron reflection ability, preferably at least one of Pb and Ni. The thermal neutron absorber 123 is located at the rear of the moderator 122 and is made of a material with a large cross section for thermal neutrons, preferably Li-6. By absorbing thermal neutrons that pass through the moderator 122, the thermal neutron absorber 123 reduces the content of thermal neutrons in the neutron beam N and prevents excessive doses to shallow normal tissue during treatment. As can be understood, the thermal neutron absorber 123 may be integrated with a moderator, and the material of the moderator includes Li-6. The radiation shielding 124 blocks neutrons and photons leaking from portions other than the beam path 125, and the material of the radiation shielding 124 includes at least one of a photon-shielding material and a neutron-shielding material. In a preferred embodiment, the material of the radiation shielding 124 includes lead (Pb), which is a photon-shielding material, and polyethylene (PE), which is a neutron-shielding material. The beam outlet 127 is provided at the rear of the beam path 125, and the epithermal neutron beam emitted from the beam outlet 127 is irradiated to the irradiated object, passes through shallow normal tissue, and then is slowed down to thermal neutrons and reaches tumor cells in the irradiated object M.During radiation irradiation treatment, the control module 20 retrieves a treatment plan corresponding to the current patient from the treatment planning system 10 and controls the neutron irradiation device 100 to irradiate based on the treatment plan.

[0055] In the present invention, before treatment, the subject is administered radioactively labeled boron ( 10 B)-containing drugs are incorporated and radionuclide medical imaging (e.g., PET) is performed to detect boron ( 10 B) It is necessary to obtain concentration-related information, that is, the medical image data of the irradiated area of ​​the irradiated body includes tissue-related information and boron concentration-related information. Specifically, a radionuclide medical image scanning device detects positrons generated by the decay of radionuclides and electrons in the tissue, causing a positron-electron annihilation reaction. At this time, a detector such as a photomultiplier tube (PMT) can be used to detect gamma rays emitted by the annihilation reaction. Then, a computer forms a cross-sectional image reflecting the distribution of the positron-emitting isotope to obtain boron concentration-related information. In one embodiment, 18 F-BPA-PET was used as a marker for scanning, and the raw data for each grid in the image was 18 The counting rate of photons generated by the annihilation of positrons and electrons emitted by the decay of F is converted into the image grid intensity of each grid of the PET image, and the medical image data is output. 18 Because it is labeled with F, the raw data on the PET image is 10 As can be seen, when radionuclide medical imaging is performed using a non-boron-containing drug that has similar tumor cell affinity to the radiolabeled boron-containing drug, the raw data on the image can also be used as a basis for B quantification. 10 BIt can be used as a basis for quantification.

[0056] Standard Uptake Value (SUV) is a semi-quantitative index collected from radionuclide medical images and refers to the ratio of the radioactivity of the contrast agent (radiolabeled drug) taken up in the local tissue to the systemic average administered activity, and is specifically defined by Equation 1.

number

[0057] In a first embodiment, the radionuclide medical image is a PET image, and the radiolabeled boron-containing drug incorporated into the irradiated subject is 18 F-BPA. 18 F-BPA may be replaced by other radiolabeled drugs or other boron-containing drugs, and non-boron-containing drugs that approximate the tumor cell affinity of the radiolabeled boron-containing drugs, e.g., 18 It may also be F-FDG.

[0058] As shown in FIG. 5, a treatment plan generation method is provided based on a boron neutron capture therapy system, and the treatment plan generation method includes the following steps:

[0059] A 3D voxel prosthetic tissue model with tissue type and tissue density data is established.

[0060] According to the tissue-related information of the medical image data of the irradiated area, a 3D voxel prosthesis tissue model having tissue type and tissue density data is correspondingly established, as shown in Figure 6, specifically: a step of reading medical image data, where the medical image data is usually in DICOM (Digital Imaging and Communications in Medicine) format, and the DICOM data includes information such as the subject's body weight, the administered drug dose, the drug activity measurement time, the contrast time, the radionuclide half-life, and the drug type, which can be determined when starting the radionuclide medical image scan, and the information source can be manually entered by the operator or can be automatically acquired or retrieved; establishing a three-dimensional medical image voxel model; defining a boundary of a region of interest; Defining the tissue type (elemental composition) and tissue density of each voxel unit.

[0061] This may be defined automatically based on a transformation relationship between CT image data and tissue type and tissue density, or may be defined manually by the user, for example, by assigning a specific tissue type and tissue density to voxel units within the boundary of each region of interest.

[0062] The boron concentration is set for each voxel unit in the 3D voxel prosthetic tissue model.

[0063] Based on the boron concentration-related information in the medical image data of the irradiated area, each voxel unit in the 3D voxel prosthesis tissue model is assigned a corresponding boron concentration data. Based on the 3D voxel prosthesis tissue model labeled with the boron concentration information of the tissue, the boron-containing drug concentration in each voxel unit can be accurately determined. This allows for a more accurate reflection of the nuclear particle collision trajectory and energy distribution in the region of interest of the irradiated body during neutron irradiation simulation. The boron concentration-related information is obtained from radionuclide medical images of the irradiated area, and the radiolabeled boron-containing drug incorporated into the irradiated body is used to scan the radionuclide medical images. The treatment planning module 30 then assigns different boron concentrations to each voxel unit in the 3D voxel prosthesis tissue model based on the radionuclide medical image data and the boron concentration information. As shown in FIG. 7, the method specifically includes the following steps:

[0064] Group regions of interest based on normalized uptake values.

[0065] According to the above formula 1, the 10 The B information can be converted into SUV values ​​for quantitative analysis to obtain the maximum, minimum, and average SUV values ​​within the region of interest. The medical professional then grouped the SUV values ​​to obtain I groups. After grouping, the average SUV value of the i-th group was calculated using Equation 2, which is as follows:

number

[0066] If the area of ​​interest consists of M materials, after grouping, the total number of materials used is M total = M × I, where if I is too large, the calculation process takes a long time, and if I is too small, it will not truly reflect the actual distribution of boron in the region of interest. The system obtains drug and subject body shape parameters based on the PET image tag (DICOM tag), and obtains drug uptake and distribution information for the region of interest defined by the system user to determine the number of groups to be grouped. If the drug uptake distribution is discrete, a larger number of groups is set, and conversely, if the drug uptake distribution is uniform, a smaller number of groups is set. Typically, I ∈ [10, 500], preferably I ∈ [10, 100], and more preferably I is 40, 44, 50, 54, or 60.

[0067] In principle, the SUV values ​​within the region of interest are distributed before and after grouping. 10 The total number of B atoms remains the same, and based on this, after grouping 10 The total number of B atoms before grouping 10 Adjust the group number or average value of SUVs using Equation 3 to ensure that it approximately matches the total number of B atoms, Equation 3 is as follows:

number

number

number

[0068] After grouping 10 The total number of B atoms and the number of atoms before grouping10 The number of groups I or the average value of SUVs is adjusted by a normalization factor k until the difference from the total number of B atoms falls within a predetermined range, which in one embodiment is 5%.

[0069] As can be seen, if k is used to adjust the number of groups I, the mean value of the SUV changes accordingly, and if k is used to adjust the mean value of the SUV, the number of groups I changes accordingly.

[0070] The boron concentration in each voxel within the region of interest is determined.

[0071] Within each voxel in the region of interest 10 Number of B atoms N B10 , group(V) is calculated using Equation 4, which is as follows:

number

[0072] Obtain the dose distribution.

[0073] After defining information such as boron concentration (i.e., number of boron atoms) and density for each voxel of the region of interest in the 3D voxel prosthetic tissue model, a Monte Carlo simulation program (e.g., MCNP, Monte Carlo N Particle Transport Code) is used to perform simulations. By sampling at different irradiation angles, the physical dose rate distribution at different irradiation angles in the 3D voxel prosthetic tissue model is simulated. That is, by simulating the physical dose received per unit time by each voxel unit in the 3D voxel prosthetic tissue model under irradiation with the defined beam at the different sampled irradiation angles, the dose distribution situation is obtained, and the amount of boron generated by the capture reaction is calculated. 4 He and 7 Assuming that Li is deposited in situ, the physical dose of boron in each voxel, D B10 is calculated using Equation 5, which is as follows:

number

[0074] When sampling, the beam irradiation position and irradiation angle must be determined. The irradiation position and irradiation angle can be determined using a forward algorithm or a backward algorithm. In a forward algorithm, an extracorporeal position is determined as the irradiation position, and calculations can be performed by sequentially sampling at fixed angle or distance intervals, or by random sampling. The beam angle can be set as a vector direction from the irradiation position to the tumor's center of gravity or deepest part. In a backward algorithm, a starting position within the tumor area is determined, and the starting position can be randomly sampled within the tumor's center of gravity, deepest part, or tumor area. The beam angle can be set by random sampling or sampling at specified intervals. When sampling, the beam angle can be selected, for example, by evaluating the beam angle to select a preferred irradiation angle or to exclude irradiation angles that cannot be implemented due to equipment interference.

[0075] A treatment plan is generated by selecting a preferred irradiation angle based on the calculation results.

[0076] Using the maximum dose, average dose, or prescription dose of the region of interest as constraints, the irradiation time corresponding to the sampled irradiation angle is determined, and the equivalent dose distribution of the 3D voxel prosthetic tissue model at the sampled irradiation angle is obtained at the irradiation time.Then, using dose volume histograms (DVHs), isodose curves, dose tables, etc., simulation calculations are performed on the 3D voxel prosthetic tissue model at different irradiation angles and corresponding irradiation times to evaluate the equivalent dose distributions, and preferably, a treatment plan that is feasible and meets needs is obtained.

[0077] The treatment planning module 30 of the boron neutron capture therapy system in the first embodiment groups the region of interest based on the normalized uptake value, calculates corresponding boron concentration data for each voxel unit, and then combines medical image data and beam parameters to perform dose simulation to formulate a treatment plan, thereby making the distribution of boron atoms in the region of interest more consistent with the actual situation, improving the accuracy of model establishment and dose calculation, ensuring the accuracy of the treatment plan, and thereby guaranteeing the therapeutic effect. As can be seen, because boron-containing drugs are expensive and the patient is generally injected with boron-containing drugs only once during actual treatment, in another preferred embodiment, boron concentration information is preset when formulating a treatment plan, and the treatment plan is generated based on the preset boron concentration information.

[0078] A boron neutron capture therapy system according to a second embodiment of the present invention includes a neutron irradiation device 10, a treatment planning module 30, and a control module 40. The neutron irradiation device 10 generates a neutron beam and irradiates the neutron beam onto a target body. The treatment planning module 30 determines at least a high-concentration drug absorption region and a low-concentration drug absorption region based on a region of interest, and performs drug concentration setting and dose distribution evaluation for the high-concentration drug region and the low-concentration drug region to generate a treatment plan. The control module 40 controls the neutron irradiation device 10 to execute the treatment plan. The treatment planning module 30 includes a model establishment module, a processing module, a dose evaluation module, and a treatment plan generation module. The model establishment module, processing module, dose evaluation module, and treatment plan generation module are electrically connected in sequence, and data can be transmitted via the electrical connections.

[0079] The model establishment module establishes a three-dimensional voxel tissue model based on the medical image data. As can be appreciated, the boron neutron capture therapy system further includes an imaging device that acquires the medical image data required by the treatment planning module 30.

[0080] The medical image data is fusion image data of first image data and second image data. Specifically, the first image data is image data capable of showing the tissue contour of the irradiated body. The second image data is image data capable of showing the distribution of a drug taken into the irradiated body. The second image data is particularly radionuclide medical image data, where the drug taken or injected into the irradiated body includes a radioactive marker so that the second image data shows the distribution of the drug in the irradiated body, and the second image data includes marker parameters capable of describing the distribution of the marker.

[0081] Conventional neutron capture therapy (NCT) uses a method of setting a single boron concentration for the lesion region, which requires high accuracy in defining the region of interest. The region of interest is defined differently according to different medical images, resulting in inaccurate dose calculations. Using a single boron concentration and defining the region of interest using a single image data set leads to more inaccurate calculation results. For example, the lesion region is defined based on first image data, and a target region with high drug uptake is defined based on second image data. If the lesion region is larger than the target region, it indicates a clear lack of drug uptake in some areas within the lesion region. If the lesion region is smaller than the target region, it indicates excessive drug uptake in normal areas. Both of these cases result in deviations in dose calculations. Even if the lesion region is close to the target region, issues such as low uniformity of drug concentration distribution within the two regions can distort the estimated maximum and minimum doses.

[0082] Therefore, in the second embodiment, by defining the region of interest using the fused image, defects corresponding to different image data can be avoided, and the region of interest can be defined based on clear tissue contours and the incorporated drug distribution, thereby improving the accuracy of defining the region of interest. In addition, by combining the above-mentioned division of the region of interest into a high-concentration drug absorption region and a low-concentration drug absorption region, not only is the impact of the accuracy of defining the region of interest on dose calculation improved, but the problem of inaccurate dose calculation caused by the conventional setting of a single boron concentration is avoided, further improving the accuracy of dose assessment.

[0083] In some embodiments, the first image data is acquired by a first imaging device. The first imaging device may be a computed tomography (CT) device or a magnetic resonance (MR) device, specifically, a plain CT, a contrast-enhanced CT, a CTsim, or an MR. CT has a better imaging effect on bones, while MR has a better imaging effect on soft tissues. In this embodiment, the first imaging device may be a CTsim, because images acquired by a CTsim have higher resolution than other image acquisition devices, improving the accuracy of image registration and region definition in subsequent steps. As shown in FIG. 9 , FIG. 9 illustrates an initial lesion region defined based on a CTsim image. The first image data may not represent information data on drug distribution. When acquiring the first image data, the subject may be administered or injected with a drug containing a marker, or may be administered or injected with a drug not containing a marker.

[0084] In some embodiments, the second image data is acquired by a second imaging device, which is particularly a radionuclide medical image acquisition device. The second imaging device is a multi-mode imaging device, which includes at least a first mode unit and a second mode unit. The first mode unit can acquire a second functional image including image data of the marker parameters, and the second mode unit can acquire a second cross-sectional image. One of the first mode unit and the second mode unit can acquire or generate a transformation matrix for the second functional image and the second cross-sectional image, which can realize registration and fusion of the second functional image and the second cross-sectional image. Furthermore, the transformation matrix can be used to transform images of the same or different imaging modalities to match their spatial positions and spatial coordinates, and the characteristics of each imaging modality can be used to spatially register the two types of images, and the registered image data can be fused into a single image.

[0085] Furthermore, the multi-mode imaging device may specifically be a combination device of an emission computed tomography (ECT) device and another imaging device, such as a PET-CT device combining a positron emission tomography (PET) device with a CT, a SPECT-CT device combining a single-photon emission computed tomography (SPECT) device with a CT, or a PET-MR device combining a positron emission tomography device with a nuclear magnetic resonance device.

[0086] In some embodiments, the second imaging device and the first imaging device may be the same imaging device, which is a multi-mode imaging device, such as a PET-CT, SPECT-CT, or PET-MR, and the technician can obtain the data necessary for the first image data and the second image data from the image data output from the multi-mode imaging device.

[0087] The model establishment module can establish a three-dimensional voxel tissue model including marker parameters based on the first image data or the fused image data, where each voxel unit in the model has a corresponding drug distribution parameter and marker parameter.

[0088] The processing module defines a region of interest based on the three-dimensional voxel tissue model, determines at least a region of high drug absorption and a region of low drug absorption based on the region of interest, groups the regions of high drug absorption and the regions of low drug absorption such that the regions of high drug absorption are divided into at least one group and the regions of low drug absorption are divided into at least two groups, and sets a drug concentration for each group.

[0089] The processing module can define a region of interest, including a region requiring radiation therapy of the lesion, based on the fused image data. The processing module can accurately and automatically define the required region of interest using the fused image data based on the marker parameters included in the second image data and the clear tissue contour of the irradiated body included in the first image data. As shown in FIG. 10, FIG. 10 shows a fused image after fusing the CTsim image and the PET image, and the area surrounded by a red line in FIG. 10 is the defined region of interest. In some embodiments, the surgeon can operate the processing module 12 to define the region of interest.

[0090] The division into high-concentration drug absorption regions and low-concentration drug absorption regions is based on a specified value representing the drug concentration, and the specified value is usually determined taking into consideration the therapeutic effect.

[0091] In the high-drug absorption region, the drug uptake rate of the tissue in the region is higher, resulting in a higher drug concentration distribution. The drug concentrations of all voxel units in the high-drug absorption region are greater than the drug concentration represented by the above-mentioned specified value, the drug concentration distribution in the high-drug absorption region is highly uniform, and the result of dose calculation performed by setting a uniform drug concentration for the region closely matches the actual dose received, so the high-drug absorption region can be divided into at least one group.

[0092] In low-drug absorption regions, the drug uptake rate of the tissue in the region is lower, resulting in a lower drug distribution concentration.The drug concentrations of each voxel unit in the low-drug absorption region are all lower than the drug concentration represented by the specified value, and the drug concentration distribution range in the low-drug absorption region is wide and not uniform. Therefore, if a uniform drug concentration is directly set for the entire region and dose calculation is performed, the difference between the actual dose and the result is large. Therefore, in order to improve the accuracy and reliability of dose assessment, it is necessary to divide the low-drug absorption region into more groups and perform dose calculations for non-uniform drug concentrations, and the low-drug absorption region can be divided into at least two groups.Furthermore, the number of groups divided in the high-drug absorption region is smaller than the number of groups divided in the low-drug absorption region.

[0093] In some embodiments, the treatment planning module 30 further defines a TBR as the ratio of the drug concentration in the region of interest to the drug concentration in blood, and a TNR as the ratio of the drug concentration in the region of interest to the drug concentration in normal tissue. The processing module separates the high drug absorption region and the low drug absorption region based on the value of the TBR or TNR, and groups the high drug absorption region and the low drug absorption region based on the value of the TBR or TNR, respectively, where the value of the TBR or TNR is the specified value.

[0094] Furthermore, the processing module determines a region in the region of interest where the TBR is equal to or greater than a first designated value as a region of high drug absorption, or a region in the region of interest where the TNR is equal to or greater than a second designated value as a region of high drug absorption. The processing module determines a region in the region of interest where the TBR is smaller than the first designated value or where the TNR is smaller than a second designated value as a region of low drug absorption.

[0095] In some embodiments, the drug taken or injected by the subject is a boron drug, and if the concentration of the boron drug taken up in normal tissue is lower than the blood boron concentration, i.e., if the TNR of the same region of interest is greater than the TBR, the first specified value is 1.2 or greater and the second specified value is 1.5 or greater.

[0096] In some embodiments, the drug ingested or injected by the subject is BPA, specifically 18 For F-BPA, when the uptake status of BPA in the human body is such that the boron concentration incorporated into normal tissues is close to the boron concentration in blood, i.e., the TNR of the same region of interest is equal to the TBR, the first specified value is equal to 2.5 and the second specified value is equal to 2.5.

[0097] As can be seen, the TBR has an Nth designated value, and the TNR has an Mth designated value, where the Nth designated value and the Mth designated value divide the region of interest into N+1 or M+1 regions, where N and M are integers greater than or equal to 1. The total number of divided regions, the number of divided regions of high-concentration drug absorption regions, and the number of divided regions of low-concentration drug absorption regions can all be determined based on factors such as the type of drug, the uniformity of drug concentration distribution, the type of tumor being treated, and individual differences in the irradiated subject. The specific values ​​of the Nth designated value and the Mth designated value can be determined based on 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 being treated, and individual differences in the irradiated subject.

[0098] In a second embodiment, the processing module divides the regions of interest into three groups, with the high drug absorption region divided into one group, designated as the first region, and the low drug absorption region divided into two groups, designated as the second and third regions. The regions of the low drug absorption region where the TBR is equal to or greater than a third designated value or the TNR is equal to or greater than a fourth designated value are the second region, and the regions of the low drug absorption region where the TBR is less than the third designated value or the TNR is less than the fourth designated value are the third region. The third designated value is greater than 1.5 and less than 2.0, and the fourth designated value is equal to the third designated value. Furthermore, if the drug is BPA, the third designated value is equal to the fourth designated value, which is equal to 2.0. As can be understood, the first, second, third, and fourth designated values ​​are all TBR or TNR values.

[0099] By injecting a drug labeled with a marker into the irradiated subject and acquiring second image data, the uptake and distribution of the drug can be observed and acquired. Since the marker does not affect the pharmacokinetics of the drug itself, the drug distribution status using a radionuclide-containing marker is quite reliable.

[0100] In the embodiments described herein, the TBR or TNR is obtained based on radionuclide medical images, such as PET images, and further grouped into regions of interest, so the drug injected into the irradiated subject is a drug labeled with a radionuclide. In other embodiments, the TBR or TNR may not be obtained by medical images, and the drug concentration may be measured by blood sampling or tissue extraction, in which case the injected drug may be a regular drug that is not labeled with a radionuclide.

[0101] The treatment planning module 30 further converts the drug concentration into one of the following values: the radioactivity of the marker, the radioactivity intensity of the marker, the number of atoms decaying per unit time, the effective count of photons generated by annihilation, and the standardized uptake value, all of which are obtained based on the medical image data, and performs quantitative or semi-quantitative analysis to obtain a quantitative or semi-quantitative parameter of the corresponding marker, which is defined as the marker parameter, and the specified value is the marker parameter. In some embodiments, the imaging device can directly obtain the marker parameter from the second image data or the fusion image data. Preferably, the radionuclide-containing marker is: 18 It may be F.

[0102] Based on the second image data, which is a PET image in this embodiment, the standardized uptake value SUV of each region can be obtained, and the TBR and TNR are calculated by the following equations (1) and (2), respectively.

number

number

[0103] The processing module assigns a drug concentration to each group of regions, and in some embodiments, a uniform drug concentration is assigned to each group of regions. Specifically, the TBR or TNR of each voxel unit in the Vth region is averaged based on the tumor volume within the region, and the calculated result is used as the average designated value. Based on the average designated value, a uniform drug concentration is determined for the region, which serves as the basis for dose distribution evaluation.

[0104] Furthermore, if the drug is a radionuclide labeled boron drug, the treatment planning module 30 calculates the boron concentration N B10 The values ​​are converted into standardized uptake values ​​(SUV) for quantitative analysis.

number

number

[0105] In some embodiments, the dose assessment module performs dose assessment based on the drug concentration and the irradiation parameters of the neutron beam. The treatment plan generation module generates a treatment plan based on the result of the dose assessment.

[0106] The dose evaluation module uses a pre-configured Monte Carlo simulation program to simulate the nuclear particle collision trajectories and energy distribution in the internal 3D space when a neutron beam is irradiated onto a patient during BNCT. This simulates the physical dose rate distribution and calculates the equivalent dose rate distribution based on the physical dose rate distribution. The Monte Carlo simulation program defines the neutron beam irradiation parameters (e.g., beam energy, intensity, radius, etc.) and simulates the physical dose received per unit time for each voxel unit in the 3D voxel tissue model using the defined irradiation parameters. In BNCT treatment dose calculations, the main factors contributing to the dose are boron dose and neutron dose. To more intuitively evaluate the BNCT dose, different weighting factors, such as RBE and CBE, are applied to the dose composition, and the biologically equivalent dose is calculated using the weighting factor, as shown in Equation 7 below.

number

[0107] In some embodiments, mathematical algorithms such as dose volume histograms (DVH), isodose curves, and dose tables can be used to evaluate equivalent dose distributions obtained by performing simulation calculations on a 3D voxel tissue model.

[0108] FIG. 8 shows a flowchart of a dose evaluation method for a boron neutron capture therapy system according to a second embodiment of the present application. As shown in FIG. 8, the dose evaluation method includes the following steps:

[0109] Establishing a model: Establishing a three-dimensional voxel tissue model based on medical image data of the irradiated body. Specifically, the step of establishing a three-dimensional voxel tissue model based on the medical image data includes the steps of acquiring first image data and establishing a three-dimensional voxel tissue model based on the first image data. Furthermore, the first image data is image data that can indicate the tissue contour of the irradiated body.

[0110] Defining a region of interest: defining a region of interest based on a three-dimensional voxel tissue model. Specifically, the step of defining a region of interest based on a three-dimensional voxel tissue model includes the steps of acquiring first image data, acquiring second image data, registering the first image data and the second image data to obtain fusion image data, and defining a region of interest based on the fusion image data. The first image data is CT or MRI, and the second image data is radionuclide medical image data.

[0111] As can be appreciated, the steps of establishing a three-dimensional voxel tissue model based on the first image data, acquiring the second image data, and acquiring the fused image data are not in any particular order, and as can be appreciated, the three-dimensional voxel tissue model can also be established based on the fused image data.

[0112] Dividing and grouping regions: At least high-concentration drug absorption regions and low-concentration drug absorption regions are determined based on the region of interest, and the high-concentration drug absorption regions and low-concentration drug absorption regions are grouped so that the high-concentration drug absorption regions are divided into at least one group and the low-concentration drug absorption regions are divided into at least two groups, and a drug concentration is set for each group.

[0113] Specifically, the step of dividing and grouping the regions includes: A step of dividing regions based on TBR or TNR, in which TBR is defined as the ratio of the drug concentration in the region of interest to the drug concentration in blood, TNR is defined as the ratio of the drug concentration in the region of interest to the drug concentration in normal tissue, and a region of the region of interest where the TBR is equal to or greater than a first designated value or where the TNR is equal to or greater than a second designated value is determined as a high-concentration drug absorption region, and a region of the region of interest where the TBR is smaller than the first designated value or where the TNR is smaller than the second designated value is determined as a low-concentration drug absorption region; and determining a designated value based on the drug, wherein if the drug is a boron drug, the first designated value is 1.2 or greater and the second designated value is 1.5 or greater, and if the drug is BPA, the first designated value is equal to the second designated value, i.e., 2.5. Furthermore, if the drug is BPA, dividing the region based on the TBR or TNR includes dividing the region of interest into three groups, where the region of high drug absorption is divided into one group as a first region and the region of low drug absorption is divided into two groups as a second region and a third region, respectively, where the region of low drug absorption where the TBR is equal to or greater than the third designated value or the TNR is equal to or greater than a fourth designated value is the second region, and the region of low drug absorption where the TBR is less than the third designated value or the TNR is less than the fourth designated value is the third region, where the third designated value is equal to the fourth designated value, i.e., 2.0.

[0114] In some embodiments, the subject is a brain tumor patient, and the tumor volume GTV of the patient is anatomy The area of ​​interest is large, and the volume of the region of interest is 155.9 cc, i.e., GTV anatomy The patient was given a boron drug.18 When F-BPA is injected and the TBR obtained from the image data ranges from 0.70 to 5.95, the first designated value is set to 2.5, and the region where TBR is ≥ 2.5 is defined as the high-drug absorption region (Region 1), as shown in Figure 11. The red region surrounded by a green line in Figure 11 corresponds to Region 1, and the region where TBR is < 2.5 is defined as the low-drug absorption region. The third designated value is set to 2.0, and the low-drug absorption region is divided into Region 2 where TBR is ≤ 2.5 and Region 3 where TBR is < 2.0. The orange region surrounded by a yellow line in Figure 11 corresponds to Region 2, and the green region surrounded by a red line corresponds to Region 3.

[0115] Drug concentration setting: tumor volume within the Vth region (GTV) anatomy The TBR or TNR of each voxel unit in the region is averaged based on the above equation to obtain a uniform boron concentration in the region.

[0116] In the above patient example, the tumor volume GTV1 in the divided first region is 60.8 cc, and the average designated value (i.e., average TBR) in the region calculated based on the TBR volume histogram shown in Figure 12 is 3.30, the tumor volume GTV2 in the second region is 63.0 cc, and the average TBR in the region calculated based on Figure 12 is 2.26, and the tumor volume GTV3 in the third region is 35.1 cc, and the average TBR in the region calculated based on Figure 12 is 1.67. Because the distribution of the set boron concentrations is uniform, each of the average TBRs corresponds to one boron concentration value.

[0117] Dose assessment: Dose assessment is performed based on drug concentration and neutron beam irradiation parameters.

[0118] Specifically, the step of dose assessment includes a step of calculating the exposure dose based on the drug concentration and the exposure parameters of the neutron beam.

[0119] The results of calculating the dose function for the above patient with a non-uniform boron concentration distribution using the conventional treatment planning system NeuMANTA are used as a control calculation group, and are compared with the dose evaluation results of the second embodiment. anatomy All the boron concentrations in the 132 regions are assigned and grouped, and the boron concentrations of the 132 regions are set, which is anatomy This corresponds to dividing the GTV into 132 regions and calculating the dose for a uniform boron concentration distribution. anatomy The dose calculation for uniform boron concentration distribution is performed by dividing the area into three regions.

[0120] The dose calculation time in the second embodiment is nearly 80% shorter than that of the control group. This is because the difference in boron concentration between some of the 132 regions in the control group calculation is small. The difference in the set boron concentration has little impact on the dose calculation, but it increases the calculation time and occupies a large amount of memory. The method of dividing and grouping regions in the second embodiment of the present application significantly reduces the dose calculation time while ensuring high reliability and accuracy of the dose results. It also reduces the time used to develop the treatment plan, reduces the requirements and dependency on hardware equipment of the treatment planning system 10, and improves the convenience of the treatment process. GTV of the second embodiment of the present application and the control group anatomy The dose results and differences are shown in Figure 13 and in the table below. [Table 1] In the table, D max is the maximum dose obtained in the simulated treatment calculation of the patient, and D min is the minimum dose obtained in the simulated treatment calculation of the patient, and D mean is the average dose obtained in the simulated treatment calculation of the patient, and D 80is the dose obtained at 80% of the lesion volume, in Gy-Eq. In FIG. 13, the solid line indicates the dose-volume histogram for the method of the second embodiment of the present invention, and the dashed line indicates the dose-volume histogram for the method of the control group. The abscissa Dose (Gy-Eq) is the irradiation dose, and the ordinate Volume (%) is the percentage of the lesion volume.

[0121] As can be seen from the above table and Figure 13, the DVH distributions of the two methods have a good agreement. min , D mean and D 80 The deviation between the calculation result of the second embodiment of the present invention and the calculation result of the non-uniform boron concentration is less than 15%, especially D mean and D 80 In this study, the deviation between the calculated results for uniform boron concentration and the calculated results for non-uniform boron concentration is less than 5%. In order to control the lesion well in actual treatment, the dose in actual treatment should always be based on a low dose, for example, the dose D obtained at 80% of the lesion volume. 80 This can ensure that the lesion receives a sufficient prescribed dose and reduces the impact on the patient's health. 80 Using this as the evaluation criterion, the calculation results of the examples of the present application have a smaller deviation than the calculation results of the control group with non-uniform boron concentration, so the method of the present application can save calculation time and ensure the accuracy of dose calculation.

[0122] As can be appreciated, the above dosimetric evaluation method can be applied and implemented in a boron neutron capture therapy system.

[0123] Although the steps in the flowcharts according to the above-described embodiments are displayed in order according to the direction of the arrows, it should be understood that these steps are not necessarily performed in the order indicated by the arrows. Unless explicitly stated otherwise in this specification, the execution of these steps is not limited to a strict order, and these steps may be performed in other orders. Furthermore, at least some of the steps in the flowcharts according to the above-described embodiments may include multiple steps or multiple stages, and these steps or stages are not necessarily performed and completed at the same time but may be performed at different times. These steps or stages are not necessarily performed sequentially, but may be performed in order or alternately with other steps or stages, or at least some of other steps or stages.

[0124] The technical features of the above examples can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above examples are described. However, as long as there is no contradiction in the combination of these technical features, any combination should be considered within the scope of the present specification. The above examples merely illustrate some embodiments of the present application, and although the descriptions are specific and detailed, they should not be construed as limiting the scope of the claims of the present application. It should be noted that a person skilled in the art can make further modifications and improvements without departing from the concept of the present application, all of which fall within the scope of protection of the present application. Therefore, the scope of protection of the present application should be determined based on the scope of the appended claims. [Explanation of symbols]

[0125] 100 Boron Neutron Capture Therapy System 10 Neutron beam irradiation equipment 11 Neutron Generator 12 Treatment table 20 Image Acquisition Module 30 Treatment Planning Module 40 Control Module 100 Neutron irradiation device 110 Radiation Generator 111 Accelerator 112 Beam Transport Device 120 Beam Shaper 126 Collimator 121 Reflector 122 Reducer 123 Thermal Neutron Absorber 124 Radiation Shielding 125 Beam Passage

Claims

1. a neutron beam irradiation device, a treatment planning module, and a control module; The neutron beam irradiation device generates a neutron beam and irradiates the neutron beam onto an irradiation target, the treatment planning module generates a treatment plan by setting a boron concentration for each voxel unit in the three-dimensional voxel prosthetic tissue model; The boron neutron capture therapy system is characterized in that the control module controls the neutron beam irradiation device based on the irradiation treatment plan.

2. 2. The boron neutron capture therapy system of claim 1, wherein the treatment planning module groups regions of interest in the three-dimensional voxel prosthetic tissue model based on normalized uptake values ​​and calculates an average value of normalized uptake values ​​within the regions of interest in each group.

3. 3. The boron neutron capture therapy system of claim 2, wherein the average value of the standardized uptake value SUV for each group is calculated using Equation 2. [Equation 1] (Formula 2) (where I is the number of groups, which is set to an even number in one embodiment of the present invention, and SUV ＲＯＩ，ｕｐｐｅｒ is the upper limit of the SUV value within the region of interest, and SUV ＲＯＩ，ｌｏｗｅｒ is the lower limit of the SUV value within the region of interest.)

4. 4. The boron neutron capture therapy system according to claim 3, wherein the number of groups I is 10 or more and 500 or less.

5. 4. The boron neutron capture therapy system according to claim 3, wherein the number of groups I is 10 or more and 100 or less.

6. 4. The boron neutron capture therapy system of claim 3, wherein the number of groups I is equal to 40, 44, 50, 54, or 60.

7. 4. The boron neutron capture therapy system of claim 3, wherein the treatment planning module adjusts the number of groups I or the average value of SUVs based on a normalization factor k, where the normalization factor k is calculated using Equation 3. [Equation 2] (Formula 3) (In the formula, SUV ＲＯＩ (V) is the SUV value of the Vth voxel in the region of interest; [Equation 3] is the total SUV value before grouping, and N ｉ is the count of the i-th group, k is the normalization factor, [Equation 4] is the SUV total value after grouping.)

8. The treatment planning module calculates the boron concentration N in each voxel in the region of interest based on Equation 4. Ｂ１０ 8. The boron neutron capture therapy system of claim 7, wherein: [Equation 5] (Formula 4) (where ξ is the SUV value corresponding １０ is a constant conversion coefficient for converting to the number of B atoms, i represents the group index, and SUV ＲＯＩ (V) is the SUV value of the Vth voxel in the region of interest.

9. 2. The boron neutron capture therapy system of claim 1, wherein the treatment planning module determines 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, and performs drug concentration setting and dose evaluation for the high-concentration drug absorption region and the low-concentration drug absorption region to generate a treatment plan.

10. the treatment planning module includes a model establishment module, a processing module, a dose evaluation module, and a treatment plan generation module; the model establishment module establishes a three-dimensional voxel tissue model based on the medical image data of the irradiated object; the processing module defines a region of interest based on the three-dimensional voxel tissue model; determines at least a region of high drug absorption and a region of low drug absorption based on the region of interest; groups the regions of high drug absorption and the regions of low drug absorption such that the regions of high drug absorption are divided into at least one group and the regions of low drug absorption are divided into at least two groups; and sets a drug concentration for each group; the dose evaluation module performs dose evaluation based on the drug concentration and the irradiation parameters of the neutron beam; The boron neutron capture therapy system of claim 9 , wherein the treatment plan generation module generates a treatment plan based on a result of the dose evaluation.

11. The treatment planning module further defines a TBR as a ratio of the drug concentration in the region of interest to the drug concentration in blood, and a TNR as a ratio of the drug concentration in the region of interest to the drug concentration in normal tissue; The boron neutron capture therapy system of claim 10, wherein the processing module determines a region of the region of interest where the TBR is equal to or greater than a first specified value or where the TNR is equal to or greater than a second specified value as the high concentration drug absorption region, and determines a region of the region of interest where the TBR is less than the first specified value or where the TNR is less than the second specified value as the low concentration drug absorption region.

12. 12. The boron neutron capture therapy system of claim 11, wherein the drug is a boron drug, the first specified value is 1.2 or greater, and the second specified value is 1.5 or greater.

13. 13. The boron neutron capture therapy system of claim 12, wherein the drug is BPA, the first specified value is equal to 2.5, and the second specified value is equal to 2.

5.

14. 14. The boron neutron capture therapy system of claim 13, wherein the processing module divides the region of interest into three groups, wherein the high drug absorption region is divided into one group as a first region, and the low drug absorption region is divided into two groups as a second region and a third region, respectively; the region of the low drug absorption region where TBR is equal to or greater than a third designated value or where TNR is equal to or greater than a fourth designated value is the second region; the region of the low drug absorption region where TBR is less than the third designated value or where TNR is less than the fourth designated value is the third region; the third designated value is greater than 1.5 and less than 2.0, and the fourth designated value is equal to the third designated value.

15. 15. The boron neutron capture therapy system of claim 14, wherein the fourth specified value is equal to the third specified value and is equal to 2.

0.

16. 13. The boron neutron capture therapy system according to claim 12, wherein the drug is a boron drug labeled with a radioactive nuclide, and the treatment planning module further converts the drug concentration into one value of the radioactivity of the marker, the radioactivity intensity of the marker, the number of atoms decaying per unit time, the effective count of photons generated by annihilation, and the standardized uptake value, all of which are acquired based on medical image data, to perform quantitative analysis or semi-quantitative analysis.

17. 17. The boron neutron capture therapy system of claim 16, wherein the treatment planning module converts the drug concentrations into standardized uptake values ​​(SUV) for quantitative analysis. [Equation 6] (Formula 6) (In the formula, N Ｂ１０ (V) is the Vth region １０ represents the number of B atoms, ξ is a constant conversion factor, [Equation 7] is the average value of the SUV of the Vth region of interest.

18. establishing a three-dimensional voxel prosthetic tissue model having tissue type and tissue density data; setting a boron concentration for each voxel unit in the three-dimensional voxel prosthetic tissue model; performing dose evaluation based on the set boron concentration and neutron beam irradiation parameters to obtain a dose distribution; and generating a treatment plan by selecting a preferred irradiation angle based on the calculation result.

19. Establishing a three-dimensional voxel prosthetic tissue model having tissue type and tissue density data includes: reading medical image data; establishing a three-dimensional medical image voxel model; defining a boundary of a region of interest; and defining a tissue type (elemental composition) and tissue density for each voxel unit.

20. The step of setting a boron concentration for each voxel unit in the three-dimensional voxel prosthetic tissue model comprises: grouping regions of interest based on normalized uptake values; and determining a boron concentration in each voxel within the region of interest.

21. The step of grouping the regions of interest is performed by: １０ 21. The method of claim 20, further comprising converting B information into SUV values, wherein Equation 1 is as follows: [Equation 8] (Formula 1) (where ROI is a region of interest defined in the image, Activity Concentration in ROI is the average radioactivity per unit volume within the region of interest, Injected Dose is the administered radioactivity, and body weight is the body weight of the irradiated subject.)

22. The dose assessment method includes: establishing a three-dimensional voxel tissue model based on medical image data of the irradiated object; 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, grouping the high-concentration drug absorption region and the low-concentration drug absorption region so that 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 setting a drug concentration for each group; 20. The method for generating a treatment plan according to claim 18, further comprising: a step of performing dose evaluation based on the drug concentration and irradiation parameters of the neutron beam.

23. 23. The treatment plan generation method of claim 22, wherein the step of determining at least a region of high drug absorption and a region of low drug absorption based on the region of interest includes the steps of defining TBR as a ratio of the drug concentration in the region of interest to the drug concentration in blood, defining TNR as a ratio of the drug concentration in the region of interest to the drug concentration in normal tissue, determining a region of the region of interest where TBR is equal to or greater than a first specified value or where TNR is equal to or greater than a second specified value as the region of high drug absorption, and determining a region of the region of interest where TBR is smaller than the first specified value or where TNR is smaller than the second specified value as the region of low drug absorption.

24. 24. The method of claim 23, wherein the drug is a boron drug, the first specified value is 1.2 or greater, and the second specified value is 1.5 or greater.

25. 25. The method of claim 24, wherein the drug is BPA, and the first specified value is equal to the second specified value, which is 2.

5.

26. 26. The treatment plan generation method of claim 25, wherein the region of interest is divided into three groups, wherein the high concentration drug absorption region is divided into one group designated as the first region, and the low concentration drug absorption region is divided into two groups designated as the second and third regions, and the region in the low concentration drug absorption region where the TBR is equal to or greater than a third designated value or the TNR is equal to or greater than a fourth designated value is the second region, and the region in the low concentration drug absorption region where the TBR is smaller than the third designated value or the TNR is smaller than the fourth designated value is the third region, and the third designated value is equal to the fourth designated value, and the third designated value is greater than 1.5 and less than 2.

0.

27. 27. The method for generating a treatment plan according to claim 26, wherein the drug is a boron drug labeled with a radioactive nuclide, and the drug concentration is converted into a standardized uptake value (SUV) for quantitative analysis. [Equation 9] (Formula 6) (In the formula, N Ｂ１０ (V) is the Vth region １０ represents the number of B atoms, ξ is a constant conversion factor, [Equation 10] is the average value of the SUV of the Vth region of interest.

Images