An equivalent biological dose calculation and plan optimization method and system

Abstract

The application discloses an equivalent biological dose calculation and plan optimization method and system, and the method comprises the following steps: determining dose objective functions and constraint conditions of target regions and radiation risk organs, and setting parameters of loss functions of the target regions and the radiation risk organs; calculating physical doses and irradiation times of each voxel based on parameters of a current radiotherapy machine and by using a dose calculation method; calculating equivalent biological doses of each voxel according to the physical doses and the irradiation times of each voxel; and calculating loss functions based on a statistical equivalent biological dose distribution state and according to the objective functions and the constraint conditions, so as to optimize the parameters of the radiotherapy machine by using a preset optimization algorithm. The application can solve the technical problem of how to utilize the FLASH effect in treatment planning, protect normal tissues and enhance tumor killing.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of radiotherapy planning, in particular to an equivalent biological dose calculation and plan optimization method and system. BACKGROUND

[0002] In 2014, the French Curie Institute discovered the FLASH effect by irradiating experimental animals with ultra-high dose rate rays. After that, the radiotherapy community began to study radiotherapy using the FLASH effect, which is called FLASH radiotherapy or ultra-high dose rate radiotherapy. The biggest feature of FLASH radiotherapy is to use the FLASH effect produced by ultra-high dose rays (generally considered > 40 Gy / s) to achieve the protection of normal tissues while not affecting tumor killing. FLASH radiotherapy was first implemented using an electron beam, and then using protons, carbon ions, etc. The research group of Tsinghua University also implemented an ultra-high dose rate X-ray accelerating tube for FLASH radiotherapy.

[0003] How to use the FLASH effect to protect normal tissues and enhance tumor killing in treatment planning is a problem that has not been solved. Existing researches are to optimize the distribution of dose rate so that the dose-weighted average dose rate or other dose rate indicators exceed a certain threshold. However, this optimization method only considers the impact of dose rate and does not consider the impact of dose and other factors. SUMMARY

[0004] The present application aims to at least solve one of the problems in the related art.

[0005] The present application proposes an equivalent biological dose calculation and plan optimization method, which helps to improve the safety and effectiveness of treatment and reduce the occurrence of side effects. Accurate dose calculation is crucial for implementing personalized treatment plans, which can ensure that each patient can obtain the best treatment effect.

[0006] Another object of the present application is to propose an equivalent biological dose calculation and plan optimization system.

[0007] To achieve the above object, the present application proposes an equivalent biological dose calculation and plan optimization method, which comprises:

[0008] Determine the dose objective function and constraint condition of the target area and the radiation at-risk organ, and set the parameters of the loss function of each target area and radiation at-risk organ;

[0009] Based on the parameters of the current radiotherapy machine, calculate the physical dose and irradiation time of each voxel using a dose calculation method;

[0010] Calculate the equivalent biological dose of each voxel according to the physical dose and irradiation time of each voxel;

[0011] Based on the distribution state of the equivalent biological dose, a loss function is calculated according to a target function and a constraint condition, so as to optimize the parameters of the radiotherapy machine by using a preset optimization algorithm.

[0012] The equivalent biological dose calculation and plan optimization method of the embodiment of the present application can further have the following additional technical features:

[0013] In an embodiment of the present application, the equivalent biological dose of each voxel is calculated according to the physical dose and irradiation time of each voxel, comprising:

[0014] The physiological parameter distribution is obtained based on the medical imaging result, wherein the physiological parameter distribution comprises the distribution of oxygen concentration and antioxidant concentration in the patient's body;

[0015] The oxygen concentration and / or antioxidant concentration are taken as the physiological parameter, and the dose and / or irradiation time at one FLASH beam-out time are taken as the physical parameter;

[0016] The physiological parameter and the physical parameter are input into a dose modification factor formula of FLASH irradiation, and the biological dose is obtained according to the calculated dose modification factor DMF and the physical dose.

[0017] In an embodiment of the present application, the method further comprises:

[0018] Supposing that the antioxidant concentration of a certain voxel obtained according to a medical image is c, the second-order rate constant of the reaction between the antioxidant and the superoxide free radical is k, the physical dose of the voxel is D, and the irradiation time is T, the equivalent biological dose EBD is calculated by the following formula:

[0019] k1=k·c

[0020]

[0021] EBD=DMF·D

[0022] Wherein k, g2, k2, f, T m are constants irrelevant to D, T and c.

[0023] In an embodiment of the present application, the loss function is Loss(*):

[0024]

[0025] Wherein w OAR is the weight of the radiation risk organ, D i is the dose of the voxel in the risk organ region, wt arget is the weight of the target region, D j is the dose of the voxel in the target region, D targetis the expected target region dose.

[0026] In one embodiment of the present application, the method further comprises: calculating Loss(EBD) based on the equivalent biological dose EBD and the loss function Loss(*) and updating the parameters of the radiotherapy machine using an L-BFGS optimizer.

[0027] To achieve the above object, another aspect of the present application provides an equivalent biological dose calculation and plan optimization system, comprising:

[0028] An initial parameter setting module is configured to determine the objective function and constraint conditions of the dose of the target region and the radiation organs at risk and set the parameters of the loss function of each target region and radiation organ at risk;

[0029] A physical dose calculation module is configured to calculate the physical dose and irradiation time of each voxel based on the current parameters of the radiotherapy machine and using a dose calculation method;

[0030] An equivalent biological dose calculation module is configured to calculate the equivalent biological dose of each voxel according to the physical dose and irradiation time of each voxel;

[0031] A loss calculation parameter optimization module is configured to calculate the loss function according to the objective function and constraint conditions based on the distribution state of the equivalent biological dose calculated statistically and to optimize the parameters of the radiotherapy machine using a preset optimization algorithm.

[0032] The equivalent biological dose calculation and plan optimization method and system of the embodiments of the present application realize one-stop processing from image to dose to optimized radiotherapy parameters by integrating physical dose calculation, biological effect modeling and mathematical optimization, improve the quality of radiotherapy, improve the treatment results of patients, reduce the potential side effect risk, and also simplify the workflow of doctors and physicists and improve the work efficiency.

[0033] Additional aspects and advantages of the present application will be given in part in the following description, will become apparent in part from the following description, or will be learned by practice of the present application. BRIEF DESCRIPTION OF DRAWINGS

[0034] The above and / or additional aspects and advantages of the present application will become apparent and be readily understood from the following description, taken in conjunction with the accompanying drawings, in which:

[0035] Figure 1 is a flowchart of the equivalent biological dose calculation and plan optimization method according to an embodiment of the present application;

[0036] Figure 2 is a structural diagram of the equivalent biological dose calculation and plan optimization system according to an embodiment of the present application. DETAILED DESCRIPTION

[0037] It should be noted that the embodiments in the present application and the features in the embodiments can be combined with each other without conflict. The present application will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[0038] In order for those skilled in the art to better understand the present application, the technical solutions in the embodiments of the present application will be described clearly and completely below in combination with the drawings of the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, not all. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor should belong to the scope of protection of the present application.

[0039] The equivalent biological dose calculation and plan optimization method and system according to the embodiments of the present application will be described below with reference to the accompanying drawings.

[0040] Figure 1 is a flowchart of the equivalent biological dose calculation and plan optimization method according to the embodiments of the present application, as shown in the figure, the method comprises: Figure 1

[0041] S1, determining the dose objective function and constraint conditions of the target region and the radiation risk organ, and setting the parameters of the loss function of each target region and the radiation risk organ;

[0042] S2, calculating the physical dose and irradiation time of each voxel based on the parameters of the current radiotherapy machine and using the dose calculation method;

[0043] S3, calculating the equivalent biological dose of each voxel according to the physical dose and irradiation time of each voxel;

[0044] S4, calculating the loss function based on the distribution state of the equivalent biological dose and according to the objective function and constraint conditions, to optimize the parameters of the radiotherapy machine by using the preset optimization algorithm.

[0045] Specifically, the present application uses equivalent biological dose as the basis for plan optimization, which specifically includes the following steps:

[0046] (1) The radiotherapy doctors and physicists determine the dose objective function and constraint conditions of the target region and the radiation risk organ;

[0047] (2) Set the weight and other loss function parameters of each target region and the radiation risk organ;

[0048] (3) Using the current radiotherapy machine parameters, using the dose calculation algorithm / module to calculate the physical dose and irradiation time of each voxel;

[0049] ​(4) Calculate the equivalent biological dose of each voxel based on the physical dose and irradiation time of each voxel;

[0050] (5) Calculate the loss function / cost function based on the objective function and constraint conditions by statistically analyzing the distribution of the equivalent biological dose;

[0051] (6) Optimize the parameters of the radiotherapy machine using optimization algorithms (including but not limited to L-BFGS, IPOPT, genetic algorithm, etc.);

[0052] (7) Repeat (2)-(6) until the distribution and statistical characteristics of the equivalent biological dose meet the requirements, and the machine parameters at this time are the optimized radiotherapy plan.

[0053] Exemplarily, the radiotherapy machine parameters include but are not limited to energy level, field size, MLC (multi-leaf collimator) configuration, etc.

[0054] Exemplarily, a suitable dose calculation algorithm is selected, such as Monte Carlo simulation, analytical algorithm or convolution / hyper convolution algorithm. By using the selected algorithm, the physical dose received by each voxel is calculated in combination with the parameters of the radiotherapy machine and the anatomical information of the patient.

[0055] Exemplarily, each voxel refers to the smallest volume unit constituting the three-dimensional anatomical image of the patient. Each voxel has its specific spatial coordinates ((x, y, z)), and in the dose calculation process, the physical dose and irradiation time are calculated for each such voxel individually. This is done to ensure that a highly precise dose distribution can be achieved, thereby optimizing the treatment effect.

[0056] In an embodiment of the present application, the equivalent biological dose of each voxel is calculated using the X-ray FLASH radiotherapy equivalent biological effect calculation method. It can include the following steps:

[0057] Obtain the distribution of physiological parameters based on medical imaging results; wherein the distribution of physiological parameters includes the distribution of oxygen concentration and antioxidant concentration in the patient's body. The distribution of oxygen concentration and antioxidant (including but not limited to glutathione, vitamin C, etc.) concentration in the patient's body can be obtained using medical imaging (including but not limited to magnetic resonance, SPECT, PET, fluorescence imaging) and other methods;

[0058] Input oxygen concentration and antioxidant concentration as physiological parameters (both or only one as input), and input dose and irradiation time (or replace with dose rate) as physical parameters (both or only one as input) at one FLASH beam;

[0059] The physiological parameters and physical parameters are inputted into the dose modification factor formula of FLASH irradiation, and then the calculated dose modification factor DMF is multiplied by the physical dose to obtain the biological dose.

[0060] It can be understood that if the physiological parameter distribution of a patient cannot be obtained by medical imaging as an input of physiological parameters, the results of a population can be used instead of the results of an individual patient.

[0061] Further, assuming that the antioxidant concentration of a certain voxel obtained from medical images is c, the second-order rate constant of the reaction between the antioxidant and the peroxidation free radical is k, the physical dose of this voxel is D, and the irradiation time is T, the equivalent biological dose EBD can be calculated by the following formula.

[0062] k1=k·c

[0063]

[0064] EBD=DMF·D

[0065] where k, g2, k2, f, T m are constants independent of D, T, and c, which can be determined by prior calculation or experiment.

[0066] Further, M represents the machine parameters, the dose D(M) and the irradiation time T(M) of the voxel at the r position can be calculated, and the physiological parameters of the voxel are obtained from medical images or estimated results, at this time the DMF and the equivalent biological dose EBD of the voxel can be calculated.

[0067] It can be understood that in radiotherapy planning, the r position usually refers to a specific position in a three-dimensional space, which is usually represented by coordinates (r=(x, y, z)). This position corresponds to the specific location of a voxel (i.e., the smallest volume unit) in the patient's body. The voxel is the basic unit of a 3D medical image (such as a CT or MRI scan image), each voxel represents a small piece of tissue and has a specific spatial coordinate.

[0068] The loss function given by the doctor and the physicist is Loss(*), for example:

[0069]

[0070] where w OAR is the weight of the radiation risk organ, D i is the dose of the voxel in the risk organ region, wt arget is the weight of the target region, D j is the dose of the voxel in the target region, D target is the expected target region dose

[0071] Then the loss (EBD) can be calculated by substituting the distribution of EBD, and the machine parameters M are updated using the L-BFGS optimizer.

[0072] Until the EBD distribution and statistical analysis results meet the requirements of doctors and physicists, the M at this time is used as the machine parameter for the subsequent process.

[0073] According to the equivalent biological dose calculation and plan optimization method, the dose objective function and constraint conditions of the target region and the radiation risk organ are determined, and the loss function parameters of each target region and OAR are set, which ensures effective irradiation of tumor tissue while minimizing damage to surrounding healthy tissue. Precise dose calculation is crucial for achieving personalized treatment plans, ensuring that each patient receives the best treatment. The introduction of EBD improves the accuracy of dose calculation. The optimized parameter setting not only ensures high-precision irradiation of tumor regions, but also effectively reduces the impact on surrounding healthy tissue, improving overall treatment effectiveness. It can solve the technical problem of how to use FLASH effect in treatment planning to protect normal tissue and enhance tumor killing.

[0074] To achieve the above embodiments, as Figure 2 shown, the equivalent biological dose calculation and plan optimization system 10 is also provided in the embodiment, which includes:

[0075] The initial parameter setting module 100 is configured to determine the dose objective function and constraint conditions of the target region and the radiation risk organ, and set the loss function parameters of each target region and radiation risk organ;

[0076] The physical dose calculation module 200 is configured to calculate the physical dose and irradiation time of each voxel based on the current radiotherapy machine parameters and using a dose calculation method;

[0077] The equivalent biological dose calculation module 300 is configured to calculate the equivalent biological dose of each voxel according to the physical dose and irradiation time of each voxel;

[0078] The loss calculation parameter optimization module 400 is configured to calculate the loss function based on the statistical distribution of the equivalent biological dose and according to the objective function and constraint conditions, and to optimize the parameters of the radiotherapy machine using a preset optimization algorithm.

[0079] Further, the equivalent biological dose calculation module 200 is also configured to:

[0080] obtain a physiological parameter distribution based on medical imaging results; wherein the physiological parameter distribution includes the distribution of oxygen concentration and antioxidant concentration in the patient's body;

[0081] The oxygen concentration and / or the antioxidant concentration are taken as the physiological parameter, and the dose and / or the irradiation time at the time of the first FLASH beam are taken as the physical parameter.

[0082] The physiological parameter and the physical parameter are input into a dose modification factor formula of FLASH irradiation, and a biological dose is obtained according to the calculated dose modification factor DMF and the physical dose.

[0083] Further, the system is further used for:

[0084] Suppose that the antioxidant concentration of a certain voxel obtained according to a medical image is c, the second-order rate constant of the reaction of the antioxidant with the peroxidation free radical is k, the physical dose of the voxel is D, and the irradiation time is T, the equivalent biological dose EBD is calculated according to the following formula:

[0085] k1=k·c

[0086]

[0087] EBD=DMF·D

[0088] wherein k, g2, k2, f, T m are constants irrelevant to D, T, and c.

[0089] Further, the loss function is Loss(*):

[0090]

[0091] wherein w OAR is the weight of a radiation critical organ, D i is the dose of a voxel in the critical organ region, wt arget is the weight of a target region, D j is the dose of a voxel in the target region, and D target is the expected dose of the target region.

[0092] Further, the system is further used for: calculating Loss(EBD) based on the equivalent biological dose EBD and the loss function Loss(*), and updating the parameters of the radiotherapy machine by using an L-BFGS optimizer.

[0093] According to the equivalent biological dose calculation and plan optimization system of the embodiment of the present application, by determining the dose objective function and constraint condition of the target region and the radiation risk organ, and setting the loss function parameter for each target region and OAR, effective irradiation of tumor tissue while minimizing damage to surrounding healthy tissue is ensured. Precise dose calculation is crucial for achieving a personalized treatment plan, which can ensure that each patient receives the best treatment effect. The introduction of EBD improves the accuracy of dose calculation. The optimized parameter setting not only ensures high-precision irradiation of the tumor area, but also effectively reduces the impact on surrounding healthy tissue, improving the overall treatment effect. The technical problem of how to utilize the FLASH effect in the treatment plan to protect normal tissue and enhance tumor killing can be solved.

[0094] In the description of the present specification, the description of the terms "one embodiment", "some embodiments", "an example", "a specific example", or "some examples" and the like means that the specific features, structures, materials or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present application. In the present specification, the illustrative description of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any appropriate manner in any one or more embodiments or examples. In addition, different embodiments or examples described in the present specification and the features of different embodiments or examples can be combined and combined by those skilled in the art without contradiction.

[0095] In addition, the terms "first", "second" are only for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of indicated technical features. Therefore, the features defined with "first", "second" can explicitly or implicitly include at least one of the features. In the description of the present application, the meaning of "a plurality of" is at least two, for example, two, three, etc., unless otherwise specifically limited.

Claims

1. An equivalent biological dose calculation and plan optimization method, characterized in that, The method comprises the following steps: determining dose objective functions and constraint conditions of target regions and radiation organs at risk, and setting parameters of loss functions of the target regions and the radiation organs at risk; calculating physical doses and irradiation times of each voxel based on parameters of a current radiotherapy machine and using a dose calculation method; calculating equivalent biological doses of each voxel according to the physical doses and the irradiation times of each voxel, comprising: obtaining a physiological parameter distribution based on medical imaging results; wherein the physiological parameter distribution comprises distributions of oxygen concentration and antioxidant concentration in a patient; taking the oxygen concentration and / or the antioxidant concentration as a physiological parameter, and taking a dose and / or an irradiation time at a time of a first FLASH beam as a physical parameter; inputting the physiological parameter and the physical parameter into a dose modification factor formula of FLASH irradiation, and obtaining a biological dose according to a calculated dose modification factor DMF and the physical dose; calculating a loss function according to the objective functions and the constraint conditions based on a statistical distribution state of the equivalent biological doses, so as to optimize parameters of the radiotherapy machine by using a preset optimization algorithm; Also included: assuming that the antioxidant concentration of a certain voxel obtained from a medical image is c , the second order rate constant of the reaction of the antioxidant with the superoxide radical is k , the physical dose of this voxel is D , the irradiation time is T , the equivalent biological dose is calculated from the following formula EBD : wherein k , g 2, k 2, f , T m are constants independent of D , T , c .

2. The method of claim 1, wherein, the loss function is Loss(*): wherein, w OAR is the weight of the organ at risk, D i is the dose of the voxel within the organ at risk, wt arget is the weight of the target volume, D j is the dose of the voxel of the target volume, D target is the expected target volume dose.

3. The method of claim 2, wherein, The method further comprises: calculating Loss(EBD) based on the equivalent biological dose EBD and the loss function Loss(*), and updating the parameters of the radiotherapy machine by using an L-BFGS optimizer.

4. An equivalent biological dose calculation and plan optimization system, characterized by, The method comprises the following steps: an initial parameter setting module is configured to determine dose objective functions and constraint conditions of target regions and radiation organs at risk, and set parameters of loss functions of the target regions and the radiation organs at risk; a physical dose calculation module is configured to calculate physical doses and irradiation times of each voxel based on parameters of a current radiotherapy machine and using a dose calculation method; an equivalent biological dose calculation module is configured to calculate equivalent biological doses of each voxel according to the physical doses and the irradiation times of each voxel, and is further configured to obtain a physiological parameter distribution based on medical imaging results; wherein the physiological parameter distribution comprises distributions of oxygen concentration and antioxidant concentration in a patient; take the oxygen concentration and / or the antioxidant concentration as a physiological parameter, and take a dose and / or an irradiation time at a time of a first FLASH beam as a physical parameter; input the physiological parameter and the physical parameter into a dose modification factor formula of FLASH irradiation, and obtain a biological dose according to a calculated dose modification factor DMF and the physical dose; a loss calculation parameter optimization module is configured to calculate a loss function according to the objective functions and the constraint conditions based on a statistical distribution state of the equivalent biological doses, so as to optimize parameters of the radiotherapy machine by using a preset optimization algorithm; The system is further configured to: Assuming that the antioxidant concentration of a certain voxel obtained from a medical image is c , the second order rate constant of the reaction of the antioxidant with the peroxidizing radical is k , the physical dose of this voxel is D , and the irradiation time is T , the equivalent biological dose is calculated from EBD ​ wherein k , g 2, k 2, f , T m are constants independent of D , T , c ​ 5. The system of claim 4, wherein, the loss function is Loss(*): wherein, w OAR is a weight of a radiation organ at risk, D i is a dose of a voxel within an organ at risk region, wt arget is a weight of a target volume, D j is a dose of a voxel of a target volume, D target is an expected target volume dose.

6. The system of claim 5, wherein, The system is further configured to: calculate Loss(EBD) based on the equivalent biological dose EBD and the loss function Loss(*), and update the parameters of the radiotherapy machine by using an L-BFGS optimizer.

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