A microdosimetry-based super-high dose rate ion beam radiation planning method, system, device and medium

Abstract

The present application relates to the technical field of ion beam radiation planning, and discloses a microdosimetry-based ultrahigh dose rate ion beam radiation planning method, system, device and medium. The present application is based on the energy deposition of the micron-scale ion beam radiation, quantifies the influence of the ultrahigh dose rate ion beam on the microenvironment of the irradiated cells, and then assesses the macroscopic radiation effect of the ultrahigh dose rate ion beam by linking the dependence relationship between the ultrahigh dose rate radiation effect and the change of the microenvironment of the irradiated cells, so as to finally realize a precise and reliable ultrahigh dose rate ion beam radiation planning method, improve the technical reliability, and expand the application range of the existing technology.

Description

Technical Field

[0001] This invention relates to the field of ion beam radiation planning technology, and in particular to an ultra-high dose rate ion beam radiation planning method, system, equipment and medium based on microdosimetry. Background Technology

[0002] Ion beams (such as protons and carbon ions) possess unique physical properties, enabling them to rapidly deposit energy at a certain depth to form a Bragg peak, thus finding wide application in materials science, biomedicine, and other fields. Ultra-high dose rate (FLASH) radiation is an innovative technology that delivers radiation dose at extremely high dose rates (typically exceeding 40 Gy / s) over a very short time (usually on the millisecond to second scale). Compared to traditional irradiation methods, FLASH radiation can deliver a large amount of energy in a short time, significantly reducing the total irradiation time. In recent years, the application of FLASH radiation technology in radiotherapy has attracted widespread attention, especially its potential in reducing damage to normal tissues and improving tumor killing effects. The combined application of the Bragg peak characteristics of ion beams and ultra-high dose rate FLASH irradiation technology holds great promise. However, a precise and reliable method for planning ultra-high dose rate ion beam radiation is still lacking.

[0003] Currently, ultra-high dose rate ion beam radiation planning methods based on physical parameters only achieve ultra-high dose rate ion beam radiation planning by setting physical parameters such as instantaneous dose rate or average dose rate, and cannot quantify radiation effects. To achieve the quantification of ultra-high dose rate ion beam radiation effects, more parameters need to be introduced to realize ultra-high dose rate ion beam radiation planning. Ion beam LET is an important parameter used to describe the energy deposition of ion radiation in a medium. It is defined as the energy deposited per unit path length when a charged particle penetrates the medium, and the unit is usually keV / μm. Therefore, LET describes the strength of the interaction between charged particles and medium atoms. A high LET value means that the ion beam energy deposition in the medium is dense, which usually leads to more radiation effects, such as DNA damage in cells. However, although LET is an important radiation dosimetry parameter, it has some limitations and defects. Since LET is usually an average value, while in reality, energy deposition may be extremely non-uniform at the microscopic scale, the average value cannot reflect the spatial distribution details of energy deposition; in addition, LET is only a spatial parameter and does not consider the change of energy deposition over time. For ultra-high dose rate radiation processes, the time factor can significantly affect biological effects. Furthermore, different types of particles (such as protons, alpha particles, and heavy ions) may have the same LET value, but their radiation effects differ; therefore, LET cannot distinguish the different characteristics of particle types and their different mechanisms of action in the medium. Thus, LET-based methods cannot achieve accurate and reliable ultra-high dose rate ion beam radiation planning.

[0004] Therefore, there is an urgent need for a precise and reliable method for planning ultra-high dose rate ion beam radiation. Summary of the Invention

[0005] This invention provides a method, system, device, and medium for ultra-high dose rate ion beam radiation planning based on microdosimetry, in order to overcome the shortcomings of existing technologies in achieving accurate and reliable ultra-high dose rate ion beam radiation planning.

[0006] This invention provides a method for ultra-high dose rate ion beam radiation planning based on microdosimetry, comprising:

[0007] To obtain the beam delivery parameters, micro-dosimetric spectrum, and beam delivery parameters of conventional dose rate ion beams;

[0008] Based on the microdosimetric line energy spectrum of the ultra-high dose rate ion beam, the track-average line energy and dose-average line energy of the ultra-high dose rate ion beam are obtained.

[0009] Based on the beam delivery parameters of the ultra-high dose rate ion beam, the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation was obtained;

[0010] Survival curves of irradiated cells under normoxic and hypoxic conditions after conventional dose rate ion beam irradiation were obtained. The survival curves of irradiated cells under normoxic and hypoxic conditions were fitted using a linear quadratic (LQ) model to obtain the LQ model parameters under normoxic and hypoxic conditions. Radiation sensitivity parameters were determined based on the LQ model parameters under normoxic and hypoxic conditions using calibrated biological samples. Combined with the micro-dose line energy spectrum of the ultra-high dose rate ion beam and the instantaneous oxygen concentration of irradiated cells during ultra-high dose rate ion beam irradiation, the specific energy of the ultra-high dose rate ion beam radiation field in a specific cell region was obtained, as well as the oxygen increase ratio at which the ultra-high dose rate ion beam reached the specific biological effect endpoint under normoxic and hypoxic conditions.

[0011] Based on the linear square model parameters under normoxic and hypoxic conditions, the linear square model parameters for irradiated cells when the oxygen content in the cellular microenvironment tends to 0 and ∞ were obtained.

[0012] Based on the linear square model parameters of irradiated cells when the oxygen content in the cell microenvironment tends to 0 and ∞, the effect of any change in oxygen content in the cell microenvironment on the linear square model parameters of irradiated cells was obtained.

[0013] Based on the beam delivery parameters of ultra-high dose rate ion beams and conventional dose rate ion beams, and combined with the influence of changes in oxygen content in the arbitrary cellular microenvironment on the linear square model parameters of the irradiated cells, the FLASH protection effect factor (FSE) of ultra-high dose rate ion beams is obtained. This factor is used to iteratively optimize the irradiation scheme and obtain the final ultra-high dose rate ion beam radiation plan.

[0014] In one embodiment, obtaining the track-average linear energy and dose-average linear energy of the ultra-high dose rate ion beam based on the microdosimetric linear energy spectrum of the ultra-high dose rate ion beam includes:

[0015] Based on the microdosimetric line energy spectrum of ultra-high dose rate ion beams, the track-average line energy of ultra-high dose rate ion beams is obtained using the expression for track-average line energy.

[0016] Based on the microdosimetric line energy spectrum of ultra-high dose rate ion beams, the dose-average line energy of ultra-high dose rate ion beams is obtained using the expression for dose-average line energy.

[0017] The expression for the track-average linear energy is:

[0018]

[0019] In the expression for the linear energy of the track average, Let f(y) represent the average linear energy of the ultra-high dose rate ion beam, y represent the linear energy of the ultra-high dose rate ion beam in the micro-dosimetry line energy spectrum, and f(y) represent the probability density of the ultra-high dose rate ion beam in the micro-dosimetry line energy spectrum.

[0020] The expression for the dose-average linear energy is as follows:

[0021]

[0022] In the expression for dose-average linear energy, This represents the dose-average linear energy of an ultra-high dose rate ion beam. Let represent the average linear energy of the ultra-high dose rate ion beam, y represent the linear energy of the ultra-high dose rate ion beam in the microdosimetric line energy spectrum, and f(y) represent the probability density of the ultra-high dose rate ion beam in the microdosimetric line energy spectrum.

[0023] In one embodiment, obtaining the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation based on the beam delivery parameters of the ultra-high dose rate ion beam includes:

[0024] Based on the beam delivery parameters of the ultra-high dose rate ion beam, the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation is obtained using the oxygen concentration expression, where the oxygen concentration expression is:

[0025]

[0026] In the oxygen concentration expression, O(t) represents the change in instantaneous oxygen concentration of the irradiated cells over time during ultra-high dose rate ion beam irradiation. env λ represents the ambient oxygen concentration, λ represents the rate at which the irradiated cell's intracellular environment acquires oxygen from the external environment, and t represents time. The instantaneous dose rate of the ultra-high dose rate ion beam is represented by g, the radiation oxygen depletion rate constant is represented by γ, and the instantaneous dose rate is represented by γ. The parameters for changes in cellular oxygen content are obtained from the rate at which irradiated cells acquire oxygen from the environment (λ) and the radiation oxygen depletion rate constant (g).

[0027] In one embodiment, obtaining the survival curves of irradiated cells under normoxic and hypoxic conditions after conventional dose-rate ion beam irradiation involves fitting the survival curves of irradiated cells under normoxic and hypoxic conditions using a linear square model to obtain linear square model parameters under normoxic and hypoxic conditions. Radiation sensitivity parameters are determined based on the linear square model parameters under normoxic and hypoxic conditions using calibrated biological samples. Furthermore, by combining the micro-dose line energy spectrum of the ultra-high dose-rate ion beam and the instantaneous oxygen concentration of the irradiated cells during ultra-high dose-rate ion beam irradiation, the specific energy of the ultra-high dose-rate ion beam radiation field in a specific cell region is obtained, as well as the oxygen increase ratio at which the ultra-high dose-rate ion beam reaches a specific biological effect endpoint under corresponding oxygen concentration conditions. This includes:

[0028] Survival curves of cells in the normoxic and hypoxic groups irradiated with conventional dose-rate ion beams were obtained. These survival curves were then fitted using a linear quadratic (LQ) model to obtain the LQ model parameter α under normoxic conditions. nor β nor Parameter α of the linear square model under hypoxic conditions hyp β hyp ;

[0029] The radiation sensitivity parameters s1 and s2 were determined based on the linear square model parameters under normoxic and hypoxic conditions of the calibrated biological samples, where s1 is the radius r of the radiation-sensitive microstructure region in the cell nucleus. d s2 is the radius R of the cell nucleus n ;

[0030] Based on the radiation sensitivity parameter s1, combined with the micro-dosimetric line energy spectrum of the ultra-high dose rate ion beam, the specific energy of the ultra-high dose rate ion beam radiation field in the radiation-sensitive microstructure region of the cell nucleus is obtained using the first specific energy expression.

[0031] Based on the radiation sensitivity parameter s2, combined with the micro-dosage line energy spectrum of the ultra-high dose rate ion beam, the specific energy of the ultra-high dose rate ion beam radiation field in the cell nucleus region is obtained using the second specific energy expression.

[0032] Based on the calibrated radiation biological effects, the radiation dose required to reach a specific radiation biological effect endpoint under normoxic and hypoxic conditions is determined respectively. Using the oxygenation ratio expression, the oxygenation ratio corresponding to the specific radiation biological effect endpoint is obtained.

[0033] In one implementation, the first specific energy expression is:

[0034]

[0035] In the first specific energy expression This represents the specific energy of the ultra-high dose rate ion beam radiation field in the radiation-sensitive microstructure region of the cell nucleus. The dose-average linear energy, r, represents the ultra-high dose rate ion beam. d ρ represents the radius of the radiation-sensitive microstructure region in the cell nucleus, ρ represents the density of the irradiated cell, tissue, or material, and π represents pi.

[0036] In one implementation, the second specific energy expression is:

[0037]

[0038] In the second specific energy expression, R represents the specific energy of the ultra-high dose rate ion beam radiation field in the cell nucleus region. n Represents the radius of the cell nucleus. R represents the dose-average linear energy of an ultra-high dose rate ion beam. n ρ represents the radius of the cell nucleus region, ρ represents the density of the irradiated cell, tissue, or material, and π represents pi.

[0039] In one implementation scheme, the oxygen increase ratio is expressed as follows:

[0040]

[0041] In the oxygen boost ratio expression, OER represents the oxygen boost ratio at which an ultra-high dose rate ion beam reaches a specific radiation biological effect endpoint under both normoxic and hypoxic conditions, and D... hyp D represents the ultra-high dose rate ion beam radiation dose required to reach a specific radiation biological effect endpoint under hypoxic conditions. nor This refers to the ultra-high dose rate ion beam radiation dose required to reach a specific radiation biological effect endpoint under normal oxygen conditions.

[0042] In one embodiment, the step of obtaining the linear square model parameters for the oxygen content in the cellular microenvironment tending towards 0 and the oxygen content tending towards ∞ under conventional dose rate irradiation, based on the linear square model parameters for normoxic and hypoxic conditions, includes:

[0043] Based on the linear square model parameters α under conventional dose rate irradiation conditions and normoxic conditions. nor β nor Parameter α of the linear square model under hypoxic conditions hyp β hyp The linear square model parameters were obtained for irradiated cells in the cellular microenvironment where the oxygen content tends to 0. Parameters of a linear square model where the oxygen content of irradiated cells in the cellular microenvironment tends to infinity.

[0044] Based on the squared model parameters of the oxygen content in the irradiated cells' cellular microenvironment tending towards 0. The squared model parameters of irradiated cells with oxygen content in the cellular microenvironment tending towards infinity. The specific energy of the ultra-high dose rate ion beam radiation field in the radiation-sensitive microstructure region of the cell nucleus and the specific energy of the ultra-high dose rate ion beam radiation field in the cell nucleus region were used to obtain the linear square model parameter α for the oxygen content of cells irradiated with ion beams of corresponding radiation quality tending to 0 in the cellular microenvironment. max β max The parameter α of the linear square model with oxygen content approaching infinity min β min .

[0045] In one implementation, the model parameters are based on the squared assumption that the oxygen content of irradiated cells in the cellular microenvironment tends to zero. The squared model parameters of irradiated cells with oxygen content in the cellular microenvironment tending towards infinity. And using the specific energy of the ultra-high dose rate ion beam radiation field in the radiation-sensitive microstructure region of the cell nucleus and the specific energy of the ultra-high dose rate ion beam radiation field in the cell nucleus region, the linear square model parameter α of the oxygen content in the cellular microenvironment of cells irradiated with ion beams of corresponding radiation quality tends to 0 is obtained using the first transformation equation. max β max The parameter α of the linear square model with oxygen content approaching infinity min β min The first transformation is:

[0046]

[0047] In the first transformation, α max β maxα represents the linear squared model parameters for cells irradiated by ion beams of corresponding radiation quality, where the oxygen content in the cellular microenvironment tends to zero. min β min The parameters represent the linear square model parameters for cells irradiated by ion beams of corresponding radiation qualities, where the oxygen content in the cellular microenvironment tends to infinity. This represents the specific energy of the ultra-high dose rate ion beam radiation field in the radiation-sensitive microstructure region of the cell nucleus. This represents the specific energy of the ultra-high dose rate ion beam radiation field in the cell nucleus region. These represent the squared model parameters for the oxygen content of irradiated cells in the cellular microenvironment tending towards 0. These represent the squared model parameters of the irradiated cells as the oxygen content in the cellular microenvironment tends to ∞.

[0048] In one embodiment, the step of obtaining the effect of any change in oxygen content in the cell microenvironment on the linear square model parameters of the irradiated cells when the oxygen content in the cell microenvironment tends to 0 and ∞ includes:

[0049] Based on the linear square model parameter α, the oxygen content in the cellular microenvironment of cells irradiated with ion beams of corresponding radiation quality tends to zero. max The linear square model parameter α of cells irradiated with ion beams of corresponding radiation quality in the cellular microenvironment tends to infinity. min Using the first impact expression, the first impact factor is obtained;

[0050] Based on the linear squared model parameter β, the oxygen content in the cellular microenvironment of cells irradiated with ion beams of corresponding radiation quality tends to zero. max The linear square model parameter β of cells irradiated with ion beams of corresponding radiation quality in the cellular microenvironment tends to infinity. min Using the second influence expression, the second influence factor is obtained;

[0051] The expression for the first influence is:

[0052]

[0053] The second influence expression is:

[0054]

[0055] In the formula, α(O) represents the first influence factor. This represents the second influencing factor, where O represents the partial pressure of oxygen (from the above formula). (Calculated), K represents the oxygen concentration at the midpoint of the corresponding oxygen increase ratio curve (this value can be calibrated independently or referenced from oxygen increase ratio curves reported in the literature; the K value is generally taken as 3.0), α max βmax α represents the linear squared model parameters for cells irradiated by ion beams of corresponding radiation quality, where the oxygen content in the cellular microenvironment tends to zero. min β min These represent the linear square model parameters for cells irradiated by ion beams of corresponding radiation quality, where the oxygen content in the cellular microenvironment tends to infinity.

[0056] In one implementation, the step of obtaining an irradiation scheme (FSE) for the ultra-high dose rate ion beam based on the beam delivery parameters of the ultra-high dose rate ion beam and the conventional dose rate ion beam, combined with the influence of arbitrary changes in oxygen content in the cellular microenvironment on the parameters of the cell linear square model, and using this scheme for iterative optimization to obtain the final ultra-high dose rate ion beam radiation plan, includes:

[0057] Based on the beam delivery parameters of ultra-high dose rate ion beams and conventional dose rate ion beams, and considering the influence of arbitrary changes in oxygen content in the cellular microenvironment on the linear square model parameters of cells, the linear square model parameter α for ultra-high dose rate ion beam irradiation is obtained. FLASH β FLASH The linear square model parameter α of conventional dose rate ion beam irradiation conv β conv ;

[0058] Based on the linear square model parameter α of ultra-high dose rate ion beam irradiation FLASH β FLASH The linear square model parameter α of conventional dose rate ion beam irradiation conv β conv The irradiation scheme FSE of the ultra-high dose rate ion beam is obtained, which is used to iteratively optimize the irradiation scheme and obtain the final ultra-high dose rate ion beam radiation plan.

[0059] In one implementation, based on the beam delivery parameters of ultra-high dose rate ion beams and conventional dose rate ion beams, and considering the influence of arbitrary changes in oxygen content in the cellular microenvironment on the linear square model parameters of the cells, the linear square model parameters α of ultra-high dose rate ion beam irradiation are obtained using a second transformation formula. FLASH β FLASH The linear square model parameter α of conventional dose rate ion beam irradiation conv β conv The second transformation is:

[0060]

[0061] In the second transformation formula, O(t) represents the change of instantaneous oxygen concentration of the irradiated cells with time t during ultra-high dose rate ion beam irradiation, and T represents the total irradiation time. When the instantaneous dose rate in O(t) is... When the dose rate is within the conventional range (e.g., 0.03 Gy / s), the calculation result is the linear square model parameter α for conventional dose rate ion beam irradiation. conv ,β conv ; when the instantaneous dose rate in O(t) When the FLASH dose rate is in the ultra-high dose rate range (e.g., 60 Gy / s), the calculation result is the linear square model parameter α for ultra-high dose rate ion beam irradiation. FLASH ,β FLASH α(O) represents the first influencing factor when the instantaneous oxygen concentration is O. denoted as the second influencing factor when the instantaneous oxygen concentration is O, K represents the oxygen concentration at the midpoint of the corresponding oxygen increase ratio curve, and dt represents the integral over the time variable t.

[0062] In one implementation, the linear square model parameter α of ultra-high dose rate ion beam irradiation is used. FLASH β FLASH The linear square model parameter α of conventional dose rate ion beam irradiation conv β conv Using the FSE expression, the irradiation scheme FSE for ultra-high dose rate ion beams is obtained, which is used to iteratively optimize the irradiation scheme and obtain the final ultra-high dose rate ion beam radiation plan. The FSE expression is:

[0063]

[0064] In the FSE expression, α FLASH β FLASH α represents the linear square model parameters corresponding to the ultra-high dose rate ion beam irradiation scheme; conv β conv Let S and D represent the linear square model parameters corresponding to the conventional dose-rate ion beam irradiation scheme, respectively. S represents cell viability, and D represents the line square model parameters. FLASH and D CONV These represent the ultra-high dose rate FLASH ion beam radiation dose and the conventional dose rate ion beam radiation dose required to achieve the same radiation biological effect, respectively. The calculated FSE can then be used to iteratively optimize the irradiation scheme and obtain the final ultra-high dose rate ion beam radiation plan.

[0065] This invention also provides an ultra-high dose rate ion beam radiation planning system based on microdosimetry, comprising:

[0066] The data acquisition module is used to acquire the beam delivery parameters of ultra-high dose rate ion beams, micro-dosimetry line energy spectra, and beam delivery parameters of conventional dose rate ion beams.

[0067] The first processing module is used to: obtain the track-average linear energy and dose-average linear energy of the ultra-high dose rate ion beam based on the microdosimetric linear energy spectrum of the ultra-high dose rate ion beam.

[0068] The second processing module is used to: obtain the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation based on the beam delivery parameters of the ultra-high dose rate ion beam;

[0069] The third processing module is used to: obtain the survival curves of irradiated cells under normoxic and hypoxic conditions after conventional dose rate ion beam irradiation; fit the survival curves of irradiated cells under normoxic and hypoxic conditions using a linear quadratic (LQ) model to obtain the LQ model parameters under normoxic and hypoxic conditions; determine the radiation sensitivity parameters based on the LQ model parameters under normoxic and hypoxic conditions using calibrated biological samples; and obtain the specific energy of the LQ radiation field in a specific cell region by combining the micro-dose line energy spectrum of the ultra-high dose rate ion beam and the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation, as well as the oxygen increase ratio at which the ultra-high dose rate ion beam reaches the specific biological effect endpoint under normoxic and hypoxic conditions.

[0070] The fourth processing module is used to: obtain the linear square model parameters for the oxygen content of irradiated cells tending to 0 and the oxygen content tending to ∞ in the cell microenvironment based on the linear square model parameters under normoxic and hypoxic conditions.

[0071] The fifth processing module is used to: obtain the effect of any change in oxygen content in the cell microenvironment on the linear square model parameters of the irradiated cells based on the linear square model parameters of the oxygen content in the cell microenvironment tending to 0 and ∞.

[0072] The planning module is used to: obtain the FLASH protection effect factor (FSE) of the ultra-high dose rate ion beam based on the beam delivery parameters of the ultra-high dose rate ion beam and the conventional dose rate ion beam, combined with the influence of changes in oxygen content in the arbitrary cellular microenvironment on the linear square model parameters of the irradiated cells, and use iterative optimization of the irradiation scheme to obtain the final ultra-high dose rate ion beam radiation plan.

[0073] The present invention also provides an electronic device, including a processor and a memory storing a computer program, wherein the processor executes the computer program to implement any of the above-described methods for ultra-high dose rate ion beam radiation planning based on microdosimetry.

[0074] The present invention also provides a non-transitory computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, implements any of the above-described methods for ultra-high dose rate ion beam radiation planning based on microdosimetry.

[0075] The present invention also provides a computer program product, the computer program product comprising a computer program that can be stored on a non-transitory computer-readable storage medium, and when the computer program is executed by a processor, the computer is able to execute any of the above-described ultra-high dose rate ion beam radiation planning methods based on microdosimetry.

[0076] This invention provides a method, system, device, and medium for ultra-high dose rate ion beam radiation planning based on microdosimetry. It quantifies the impact of ultra-high dose rate ion beams on the microenvironment of irradiated cells by using micrometer-scale ion beam radiation energy deposition as a foundation. Furthermore, by linking the ultra-high dose rate radiation effect with changes in the microenvironment of irradiated cells, it assesses the macroscopic radiation effect of ultra-high dose rate ion beams, ultimately achieving a precise and reliable method for ultra-high dose rate ion beam radiation planning, improving technical reliability, and expanding the application scope of existing technologies. Attached Figure Description

[0077] To more clearly illustrate the technical solutions in this invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of this invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0078] Figure 1 This is one of the flowcharts for an ultra-high dose rate ion beam radiation planning method based on microdosimetry provided by the present invention.

[0079] Figure 2 This is the second flowchart illustrating an ultra-high dose rate ion beam radiation planning method based on microdosimetry provided by the present invention.

[0080] Figure 3 This is a schematic diagram of a high dose rate ion beam radiation planning system based on microdosimetry provided by the present invention.

[0081] Figure 4 This is a schematic diagram of the structure of the electronic device provided by the present invention. Detailed Implementation

[0082] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, embodiments of this invention, and should not be construed as limiting the invention. All other embodiments obtained by those skilled in the art based on the embodiments of this invention without creative effort are within the scope of protection of this invention. In the description of this invention, it should be understood that the terminology used is for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0083] Studies have shown that FLASH radiation can significantly reduce radiation damage to normal tissues, thus normal tissues exhibit stronger tolerance to ultra-high dose rate radiation; this phenomenon is known as the "FLASH effect." Although FLASH radiation has a protective effect on normal tissues, its killing effect on tumor cells remains strong. Research has found that FLASH radiation has the following characteristics in killing tumor cells: Highly efficient energy transfer: It transfers a large amount of energy in a short time, rapidly causing fatal damage to tumor cells. Enhanced immune response: High dose rate radiation may induce a stronger immune response, helping to eliminate tumor cells. Selective killing: Because tumor cells have a weak ability to repair radiation damage, FLASH radiation can more effectively kill tumor cells while causing less damage to normal cells. Therefore, the combined application of the Bragg peak characteristics of ion beams and ultra-high dose rate FLASH irradiation technology has a very broad prospect. However, a precise and reliable method for planning ultra-high dose rate ion beam radiation is still lacking.

[0084] Microdosimetry is an effective tool for studying the distribution and effects of radiation energy at the microscopic spatial scale. By analyzing the energy deposition and radiation effects at the cellular and subcellular levels, it provides a more precise description of the biological effects of radiation. The core of microdosimetry lies in measuring and calculating the microscopic dose distribution, that is, the energy deposition within an extremely small volume (typically at the micrometer level). In the field of radiotherapy, microdosimetry provides a theoretical basis for understanding and planning the therapeutic effects of high linear density (LET) ion beam radiation (such as protons and heavy ions).

[0085] Radiation planning is a crucial step in ensuring the accuracy and safety of ultra-high dose rate ion beam radiation dose delivery. Traditional radiation planning methods mainly rely on macroscopic dose distribution, optimizing dose uniformity and target area coverage to plan the radiation for the irradiated target. However, for ultra-high dose rate ion beam irradiation, the unique dose rate effect and microscopic dose distribution characteristics necessitate more refined radiation planning methods.

[0086] To overcome the shortcomings of existing technologies, this invention provides a method, system, device, and medium for ultra-high dose rate ion beam radiation planning based on microdosimetry. The following describes the process in conjunction with... Figures 1-4 This invention describes the ultra-high dose rate ion beam radiation planning method, system, device, and medium based on microdosimetry. It should be noted that the execution entity of the ultra-high dose rate ion beam radiation planning method based on microdosimetry provided by this invention can be any terminal-side device that meets the technical requirements, such as an ultra-high dose rate ion beam radiation planning device based on microdosimetry.

[0087] Figures 1-2 This is a flowchart illustrating the ultra-high dose rate ion beam radiation planning method based on microdosimetry provided by this invention. (Refer to...) Figure 1 The present invention provides a method for ultra-high dose rate ion beam radiation planning based on microdosimetry, which may include:

[0088] Step S110: Obtain the beam delivery parameters of the ultra-high dose rate ion beam, the micro-dosimetry line energy spectrum, and the beam delivery parameters of the conventional dose rate ion beam.

[0089] Beam delivery parameters refer to the parameters sent by the system to the irradiation terminal during radiation irradiation. These parameters mainly include: beam spot position, dose, dose rate, and the time structure of the pulsed beam. Specifically, beam delivery parameters can include the beam physics characteristics of the rate ion beam generated by the ion beam device (such as a cyclotron or synchrotron), such as percentage depth dose distribution, beam spot transverse dose distribution, the time structure of beam delivery (such as pulse width, duty cycle, etc.), and the change of instantaneous dose rate over time at the pencil beam reference position. etc.

[0090] Furthermore, ion beam devices are used to generate the required ultra-high dose rate ion beams. These ion beams can be protons, heavy ions (such as carbon ions, oxygen ions, etc.), or other types of charged particles. Microdosimetry detectors (such as gas tissue equivalent proportional counters, semiconductor microdosimetry detectors, etc.) can be used to measure or Monte Carlo radiation transfer simulation servers can be used to calculate the energy deposition of each energy deposition event in a microscopic volume of the corresponding ion beam. Events are then classified according to the size of the energy deposition, and the line energy (the energy deposition per unit length of the ion beam) of each event is calculated. Based on the frequency of different line energies, a microdosimetry line energy spectrum is generated.

[0091] Step S120: Based on the microdosimetric line energy spectrum of the ultra-high dose rate ion beam, obtain the track-average line energy and dose-average line energy of the ultra-high dose rate ion beam.

[0092] In one embodiment, step S120 can obtain the track average line energy of the ultra-high dose rate ion beam based on the microdosimetric line energy spectrum of the ultra-high dose rate ion beam using the track average line energy expression; and obtain the dose average line energy of the ultra-high dose rate ion beam based on the microdosimetric line energy spectrum of the ultra-high dose rate ion beam using the dose average line energy expression.

[0093] The expression for the track-average linear energy is:

[0094]

[0095] In the expression for the linear energy of the track average, Let f(y) represent the average linear energy of the ultra-high dose rate ion beam, y represent the linear energy of the ultra-high dose rate ion beam in the micro-dosimetry line energy spectrum, and f(y) represent the probability density of the ultra-high dose rate ion beam in the micro-dosimetry line energy spectrum.

[0096] The expression for the dose-average linear energy is as follows:

[0097]

[0098] In the expression for dose-average linear energy, This represents the dose-average linear energy of an ultra-high dose rate ion beam. Let represent the average linear energy of the ultra-high dose rate ion beam, y represent the linear energy of the ultra-high dose rate ion beam in the microdosimetric line energy spectrum, and f(y) represent the probability density of the ultra-high dose rate ion beam in the microdosimetric line energy spectrum.

[0099] Step S130: Based on the beam delivery parameters of the ultra-high dose rate ion beam, obtain the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation.

[0100] In one embodiment, step S130 can obtain the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation using the oxygen concentration expression based on the beam delivery parameters of the ultra-high dose rate ion beam, wherein the oxygen concentration expression is:

[0101]

[0102] In the oxygen concentration expression, O(t) represents the change in instantaneous oxygen concentration of the irradiated cells over time during ultra-high dose rate ion beam irradiation. env λ represents the ambient oxygen concentration, λ represents the rate at which the irradiated cell's intracellular environment acquires oxygen from the external environment, and t represents time. The instantaneous dose rate of the ultra-high dose rate ion beam is represented by g, the radiation oxygen depletion rate constant is represented by γ, the calculation algebra is represented by γ, and γ represents the value based on the instantaneous dose rate. The parameters for changes in cellular oxygen content are obtained from the rate at which irradiated cells acquire oxygen from the environment (λ) and the radiation oxygen depletion rate constant (g).

[0103] Step S140: Obtain the survival curves of irradiated cells under normoxic and hypoxic conditions after conventional dose rate ion beam irradiation. Fit the survival curves of irradiated cells under normoxic and hypoxic conditions using a linear quadratic (LQ) model to obtain the LQ model parameters under normoxic and hypoxic conditions. Determine the radiation sensitivity parameters based on the LQ model parameters under normoxic and hypoxic conditions using calibrated biological samples. Combine the micro-dose line energy spectrum of the ultra-high dose rate ion beam and the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation to obtain the specific energy of the ultra-high dose rate ion beam radiation field in a specific cell region, and the oxygen increase ratio at which the ultra-high dose rate ion beam reaches the specific biological effect endpoint under normoxic and hypoxic conditions.

[0104] Specifically, a suitable cell line (such as HSG, V79 cells, etc.) can be selected for the study. Cells are cultured in a culture medium and divided into two groups: a normoxic group (under standard culture conditions, 21% O2) and a hypoxic group (under hypoxic conditions, typically 1% O2 or lower). Cells in both groups are irradiated with corresponding ion beams generated by a cyclotron or synchrotron, and survival curves are obtained using well-known cell clonal survival assays. The cell survival curves are then fitted using a linear squared (LQ) model to obtain the LQ model parameter α under normoxic conditions. nor ,β nor LQ model parameters α under hypoxic conditions hyp ,β hyp Based on the calibrated biological samples (the calibrated biological samples are the objects of observation for specific biological effects, such as cells, tissues, tumors, etc.; in this embodiment, they are irradiated cells), the corresponding radiation sensitivity parameters s1, s2, etc., are determined according to the LQ model parameters of the corresponding ion beam. Preferably, s1 and s2 can be selected as the radius r of the radiation-sensitive microstructure region in the cell nucleus. d and the radius R of the cell nucleus n In this embodiment, the specific cellular region includes the nuclear subregion and a corresponding size R. n The specific biological effects in this embodiment, including radiation biological effects, are the cell nucleus region. For cell survival, a cell survival rate of 10%, 20%, or 50% is generally used as the endpoint of the radiation biological effect. For normal tissues, such as skin fibrosis, skin desquamation, etc., are also the endpoints of the radiation effect. The specific biological effects and the endpoints of the specific biological effects can be set according to the actual situation.

[0105] In one embodiment, step S140 may include:

[0106] Survival curves of cells in the normoxic and hypoxic groups irradiated with conventional dose-rate ion beams were obtained. These survival curves were then fitted using a linear quadratic (LQ) model to obtain the LQ model parameter α under normoxic conditions. nor β nor Parameter α of the linear square model under hypoxic conditions hyp β hyp ;

[0107] The radiation sensitivity parameters s1 and s2 were determined based on the linear square model parameters under normoxic and hypoxic conditions of the calibrated biological samples, where s1 is the radius r of the radiation-sensitive microstructure region in the cell nucleus. d s2 is the radius R of the cell nucleus n ;

[0108] Based on the radiation sensitivity parameter s1, combined with the micro-dosimetric line energy spectrum of the ultra-high dose rate ion beam, the specific energy of the ultra-high dose rate ion beam radiation field in the radiation-sensitive microstructure region of the cell nucleus is obtained using the first specific energy expression.

[0109] Based on the radiation sensitivity parameter s2, combined with the micro-dosage line energy spectrum of the ultra-high dose rate ion beam, the specific energy of the ultra-high dose rate ion beam radiation field in the cell nucleus region is obtained using the second specific energy expression.

[0110] Based on the calibrated radiation biological effects, the radiation dose required to reach a specific radiation biological effect endpoint under normoxic and hypoxic conditions is determined respectively. Using the oxygenation ratio expression, the oxygenation ratio corresponding to the specific radiation biological effect endpoint is obtained.

[0111] The first specific energy expression is:

[0112]

[0113] In the first specific energy expression This represents the specific energy of the ultra-high dose rate ion beam radiation field in the radiation-sensitive microstructure region of the cell nucleus. The dose-average linear energy, r, represents the ultra-high dose rate ion beam. d ρ represents the radius of the radiation-sensitive microstructure region in the cell nucleus, ρ represents the density of the irradiated cell, tissue, or material, and π represents pi.

[0114] The expression for the second specific energy is:

[0115]

[0116] In the second specific energy expression, R represents the specific energy of the ultra-high dose rate ion beam radiation field in the cell nucleus region. n Represents the radius of the cell nucleus. R represents the dose-average linear energy of an ultra-high dose rate ion beam. n The radius of the cell nucleus region is represented by π, p represents the density of the irradiated cell, tissue, or material, and π represents pi.

[0117] The expression for the oxygen increase ratio is:

[0118]

[0119] In the oxygen boost ratio expression, OER represents the oxygen boost ratio at which an ultra-high dose rate ion beam reaches a specific radiation biological effect endpoint under both normoxic and hypoxic conditions, and D... hyp D represents the ultra-high dose rate ion beam radiation dose required to reach a specific radiation biological effect endpoint under hypoxic conditions. nor This refers to the ultra-high dose rate ion beam radiation dose required to reach a specific radiation biological effect endpoint under normal oxygen conditions.

[0120] Step S150: Based on the linear square model parameters under normoxic and hypoxic conditions, obtain the linear square model parameters for the oxygen content of the irradiated cells tending to 0 and ∞ in the cell microenvironment. In this embodiment, the cell microenvironment refers to the relevant physicochemical conditions within the cell, such as oxygen concentration and pH value.

[0121] In one embodiment, step S150 may include:

[0122] Based on the linear square model parameters α under conventional dose rate irradiation conditions and normoxic conditions. nor β nor Parameter α of the linear square model under hypoxic conditions hyp β hyp Using the first transformation equation, the parameters of the linear square model for irradiated cells where the oxygen content in the cellular microenvironment tends to zero are obtained. Parameters of a linear square model where the oxygen content of irradiated cells in the cellular microenvironment tends to infinity. The first transformation is:

[0123]

[0124]

[0125] In the first transformation, α max β max α represents the linear squared model parameters for cells irradiated by ion beams of corresponding radiation quality, where the oxygen content in the cellular microenvironment tends to zero. min β minThe parameters represent the linear square model parameters for cells irradiated by ion beams of corresponding radiation qualities, where the oxygen content in the cellular microenvironment tends to infinity. This represents the specific energy of the ultra-high dose rate ion beam radiation field in the radiation-sensitive microstructure region of the cell nucleus. This represents the specific energy of the ultra-high dose rate ion beam radiation field in the cell nucleus region. These represent the squared model parameters for the oxygen content of irradiated cells in the cellular microenvironment tending towards 0. These represent the squared model parameters of the irradiated cells as the oxygen content in the cellular microenvironment tends to ∞;

[0126] Based on the squared model parameters of the oxygen content in the irradiated cells' cellular microenvironment tending towards 0. The squared model parameters of irradiated cells with oxygen content in the cellular microenvironment tending towards infinity. The specific energy of the ultra-high dose rate ion beam radiation field in the radiation-sensitive microstructure region of the cell nucleus and the specific energy of the ultra-high dose rate ion beam radiation field in the cell nucleus region were used to obtain the linear square model parameter α for the oxygen content of cells irradiated with ion beams of corresponding radiation quality tending to 0 in the cellular microenvironment. max β max The parameter α of the linear square model with oxygen content approaching infinity min β min .

[0127] Step S160: Based on the linear square model parameters of the oxygen content of the irradiated cells tending to 0 and ∞ in the cell microenvironment, obtain the effect of any change in oxygen content in the cell microenvironment on the linear square model parameters of the irradiated cells.

[0128] In one embodiment, step S160 may include:

[0129] Based on the linear square model parameter α, the oxygen content in the cellular microenvironment of cells irradiated with ion beams of corresponding radiation quality tends to zero. max The linear square model parameter α of cells irradiated with ion beams of corresponding radiation quality in the cellular microenvironment tends to infinity. min Using the first impact expression, the first impact factor is obtained;

[0130] Based on the linear squared model parameter β, the oxygen content in the cellular microenvironment of cells irradiated with ion beams of corresponding radiation quality tends to zero. max The linear square model parameter β of cells irradiated with ion beams of corresponding radiation quality in the cellular microenvironment tends to infinity. min Using the second influence expression, the second influence factor is obtained;

[0131] The expression for the first influence is:

[0132]

[0133] The second influence expression is:

[0134]

[0135] In the formula, α(O) represents the first influence factor. This represents the second influencing factor, where O represents the partial pressure of oxygen (from the above formula). (Calculated), K represents the oxygen concentration at the midpoint of the corresponding oxygen increase ratio curve (this value can be calibrated independently or referenced from oxygen increase ratio curves reported in the literature; the K value is generally taken as 3.0), α max β max α represents the linear squared model parameters for cells irradiated by ion beams of corresponding radiation quality, where the oxygen content in the cellular microenvironment tends to zero. min β min These represent the linear square model parameters for cells irradiated by ion beams of corresponding radiation quality, where the oxygen content in the cellular microenvironment tends to infinity.

[0136] Step S170: Based on the beam delivery parameters of ultra-high dose rate ion beams and conventional dose rate ion beams, and combined with the influence of changes in oxygen content in the arbitrary cell microenvironment on the linear square model parameters of the irradiated cells, the FLASH protection effect factor FSE of ultra-high dose rate ion beams is obtained, which is used to iteratively optimize the irradiation scheme and obtain the final ultra-high dose rate ion beam radiation plan.

[0137] In one embodiment, step S170 may include:

[0138] Based on the beam delivery parameters of ultra-high dose rate ion beams and conventional dose rate ion beams, and considering the influence of arbitrary changes in oxygen content in the cellular microenvironment on the linear square model parameters of cells, the linear square model parameters α for ultra-high dose rate ion beam irradiation are obtained using the second transformation equation. FLASH β FLASH The linear square model parameter α of conventional dose rate ion beam irradiation conv β conv The second transformation is:

[0139]

[0140] In the second transformation formula, O(t) represents the change of instantaneous oxygen concentration of the irradiated cells with time t during ultra-high dose rate ion beam irradiation, and T represents the total irradiation time. When the instantaneous dose rate in O(t) is... When the dose rate is within the conventional range (e.g., 0.03 Gy / s), the calculation result is the linear square model parameter α for conventional dose rate ion beam irradiation. conv ,β conv When the instantaneous dose rate in O(t) When the FLASH dose rate is in the ultra-high dose rate range (e.g., 60 Gy / s), the calculation result is the linear square model parameter α for ultra-high dose rate ion beam irradiation. FLASH ,β FLASH α(O) represents the first influencing factor when the instantaneous oxygen concentration is O. denoted as the second influencing factor when the instantaneous oxygen concentration is O, K represents the oxygen concentration at the midpoint of the corresponding oxygen increase ratio curve, and dt represents the integral over the time variable t;

[0141] Based on the linear square model parameter α of ultra-high dose rate ion beam irradiation FLASH β FLASH The linear square model parameter α of conventional dose rate ion beam irradiation conv β conv Using the FSE expression, the irradiation scheme FSE for ultra-high dose rate ion beams is obtained, which is used to iteratively optimize the irradiation scheme and obtain the final ultra-high dose rate ion beam radiation plan. The FSE expression is:

[0142]

[0143] In the FSE expression, α FLASH β FLASH α represents the linear square model parameters corresponding to the ultra-high dose rate ion beam irradiation scheme; conv β conv Let S and D represent the linear square model parameters corresponding to the conventional dose-rate ion beam irradiation scheme, respectively. S represents cell viability, and D represents the line square model parameters. FLASH and D CONV These represent the ultra-high dose rate FLASH ion beam radiation dose and the conventional dose rate ion beam radiation dose required to achieve the same radiation biological effect, respectively. The calculated FSE can then be used to iteratively optimize the irradiation scheme and obtain the final ultra-high dose rate ion beam radiation plan.

[0144] Based on the equipment modulation capability and specific application scenario, the irradiation planning target and corresponding radiation effect can be determined. The FSE of the relevant ultra-high dose rate ion beam is calculated according to the above method. At the same time, the parameters such as the dose, dose rate, and beam delivery time of the ion beam are iteratively optimized to obtain the required radiation plan (the radiation plan generally includes ion beam energy, instantaneous dose rate, and beam delivery time structure, and may also include beam spot position, depth, and specific beam delivery equipment depending on the application scenario).

[0145] After obtaining the final ultra-high dose rate ion beam radiation plan, the irradiation plan generated in a general format can be sent and stored in the central server. The ultra-high dose rate beam irradiation implementation terminal can retrieve the radiation plan. Under specific conditions, specific beam delivery equipment can also be prepared and installed in the irradiation terminal. The terminal controls the ultra-high dose rate ion beam equipment to generate and deliver the relevant beam according to the plan to irradiate the terminal target.

[0146] This invention utilizes information on the micro-energy deposition of ion beams to accurately determine the impact of changes in the microenvironment on the radiation sensitivity of the irradiated target during ultra-high dose ion beam irradiation, and based on this, to formulate a precise and reliable ultra-high dose rate ion beam irradiation planning scheme.

[0147] One embodiment of the present invention is the planning of an ultra-high dose rate carbon ion beam radiation scheme for Chinese hamster lung cells (V79). First, the depth dose distribution of the carbon ion beam is determined, and the dose distribution of the transverse beam spot at a specific depth is measured and interpolated. After determining the instantaneous dose rate at the center point of the beam spot, the instantaneous dose rate at any transverse position can be determined based on the transverse dose distribution. The microdosimetric line energy spectrum at the corresponding depth of the carbon ion beam was calculated using a Monte Carlo radiation transfer simulation server. Referring to literature reports, the radius of the radiation-sensitive microstructure region in the V79 cell nucleus is 0.31 μm, and the radius of the nucleus region is 4.6 μm. Based on this, the specific energy of the corresponding region can be determined. and The oxygen content (O(t)) in V79 cells at any lateral position was calculated based on the instantaneous dose rate and beam delivery time structure information. Extrapolation of the LQ model parameters obtained from cell survival curves of HSG under normoxic and hypoxic conditions at conventional dose rates in the literature yielded the following results. Furthermore, based on the formula where K=3, the LQ parameters α(O) and β(O) of the cell can be determined when the oxygen content of the cell microenvironment changes. This allows for the determination of the FSE of V79 cells under a specific scheme. The parameters such as the dose, dose rate, and beam delivery time of the carbon ion beam are iteratively optimized to obtain the optimal radiation scheme. This optimal scheme is stored in a general format on the central server. The ultra-high dose rate carbon ion irradiation implementation terminal retrieves this scheme and controls the ultra-high dose rate ion beam equipment to generate and deliver the relevant beam to irradiate the V79 cells according to the scheme.

[0148] The key point of this invention is to use the microscopic energy deposition law of ion beams to plan the radiation scheme of ultra-high dose rate ion beams, to plan the radiation scheme at a more refined microscopic scale, to establish an ultra-high dose rate ion beam radiation planning method and system, and to improve the reliability of the technology.

[0149] This invention provides a method, system, device, and medium for ultra-high dose rate ion beam radiation planning based on microdosimetry. It quantifies the impact of ultra-high dose rate ion beams on the microenvironment of irradiated cells by using micron-scale ion beam radiation energy deposition as a foundation. Furthermore, by linking the ultra-high dose rate radiation effect with changes in the microenvironment of irradiated cells, it assesses the macroscopic radiation effect of ultra-high dose rate ion beams, ultimately achieving a precise and reliable method for ultra-high dose rate ion beam radiation planning and expanding the application scope of existing technologies.

[0150] The ultra-high dose rate ion beam radiation planning system based on microdosimetry provided by the present invention is described below. The ultra-high dose rate ion beam radiation planning system based on microdosimetry described below can be referred to in correspondence with the ultra-high dose rate ion beam radiation planning method based on microdosimetry described above.

[0151] Reference Figure 3 The present invention provides an ultra-high dose rate ion beam radiation planning system based on microdosimetry, which may include:

[0152] The data acquisition module is used to acquire the beam delivery parameters of ultra-high dose rate ion beams, micro-dosimetry line energy spectra, and beam delivery parameters of conventional dose rate ion beams.

[0153] The first processing module is used to: obtain the track-average linear energy and dose-average linear energy of the ultra-high dose rate ion beam based on the microdosimetric linear energy spectrum of the ultra-high dose rate ion beam.

[0154] The second processing module is used to: obtain the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation based on the beam delivery parameters of the ultra-high dose rate ion beam;

[0155] The third processing module is used to: obtain the survival curves of irradiated cells under normoxic and hypoxic conditions after conventional dose rate ion beam irradiation; fit the survival curves of irradiated cells under normoxic and hypoxic conditions using a linear quadratic (LQ) model to obtain the LQ model parameters under normoxic and hypoxic conditions; determine the radiation sensitivity parameters based on the LQ model parameters under normoxic and hypoxic conditions using calibrated biological samples; and obtain the specific energy of the LQ radiation field in a specific cell region by combining the micro-dose line energy spectrum of the ultra-high dose rate ion beam and the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation, as well as the oxygen increase ratio at which the ultra-high dose rate ion beam reaches the specific biological effect endpoint under normoxic and hypoxic conditions.

[0156] The fourth processing module is used to: obtain the linear square model parameters for the oxygen content of irradiated cells tending to 0 and the oxygen content tending to ∞ in the cell microenvironment based on the linear square model parameters under normoxic and hypoxic conditions.

[0157] The fifth processing module is used to: obtain the effect of any change in oxygen content in the cell microenvironment on the linear square model parameters of the irradiated cells based on the linear square model parameters of the oxygen content in the cell microenvironment tending to 0 and ∞.

[0158] The planning module is used to: obtain the FLASH protection effect factor (FSE) of the ultra-high dose rate ion beam based on the beam delivery parameters of the ultra-high dose rate ion beam and the conventional dose rate ion beam, combined with the influence of changes in oxygen content in the arbitrary cellular microenvironment on the linear square model parameters of the irradiated cells, and use iterative optimization of the irradiation scheme to obtain the final ultra-high dose rate ion beam radiation plan.

[0159] Figure 4 An example is a schematic diagram of the physical structure of an electronic device, such as... Figure 4 As shown, the electronic device may include: a processor 810, a communication interface 820, a memory 830, and a communication bus 840, wherein the processor 810, the communication interface 820, and the memory 830 communicate with each other via the communication bus 840. The processor 810 can call logical instructions in the memory 830 to execute a microdosimetry-based ultra-high dose rate ion beam radiation planning method, which includes:

[0160] To obtain the beam delivery parameters, micro-dosimetric spectrum, and beam delivery parameters of conventional dose rate ion beams;

[0161] Based on the microdosimetric line energy spectrum of the ultra-high dose rate ion beam, the track-average line energy and dose-average line energy of the ultra-high dose rate ion beam are obtained.

[0162] Based on the beam delivery parameters of the ultra-high dose rate ion beam, the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation was obtained;

[0163] Survival curves of irradiated cells under normoxic and hypoxic conditions after conventional dose rate ion beam irradiation were obtained. The survival curves of irradiated cells under normoxic and hypoxic conditions were fitted using a linear quadratic (LQ) model to obtain the LQ model parameters under normoxic and hypoxic conditions. Radiation sensitivity parameters were determined based on the LQ model parameters under normoxic and hypoxic conditions using calibrated biological samples. Combined with the micro-dose line energy spectrum of the ultra-high dose rate ion beam and the instantaneous oxygen concentration of irradiated cells during ultra-high dose rate ion beam irradiation, the specific energy of the ultra-high dose rate ion beam radiation field in a specific cell region was obtained, as well as the oxygen increase ratio at which the ultra-high dose rate ion beam reached the specific biological effect endpoint under normoxic and hypoxic conditions.

[0164] Based on the linear square model parameters under normoxic and hypoxic conditions, the linear square model parameters for irradiated cells when the oxygen content in the cellular microenvironment tends to 0 and ∞ were obtained.

[0165] Based on the linear square model parameters of irradiated cells when the oxygen content in the cell microenvironment tends to 0 and ∞, the effect of any change in oxygen content in the cell microenvironment on the linear square model parameters of irradiated cells was obtained.

[0166] Based on the beam delivery parameters of ultra-high dose rate ion beams and conventional dose rate ion beams, and combined with the influence of changes in oxygen content in the arbitrary cellular microenvironment on the linear square model parameters of the irradiated cells, the FLASH protection effect factor (FSE) of ultra-high dose rate ion beams is obtained. This factor is used to iteratively optimize the irradiation scheme and obtain the final ultra-high dose rate ion beam radiation plan.

[0167] Furthermore, the logical instructions in the aforementioned memory 830 can be implemented as software functional units and, when sold or used as independent products, can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of the present invention, essentially, or the part that contributes to the prior art, or a part of the technical solution, can be embodied in the form of a software product. This computer software product is stored in a storage medium and includes several instructions to cause a computer device (which may be a personal computer, server, or network device, etc.) to execute all or part of the steps of the methods described in the various embodiments of the present invention. The aforementioned storage medium includes various media capable of storing program code, such as USB flash drives, portable hard drives, read-only memory (ROM), random access memory (RAM), magnetic disks, or optical disks.

[0168] On the other hand, the present invention also provides a computer program product, the computer program product comprising a computer program that can be stored on a non-transitory computer-readable storage medium, wherein when the computer program is executed by a processor, the computer is able to execute the ultra-high dose rate ion beam radiation planning method based on microdosimetry provided by the above methods, the method comprising:

[0169] To obtain the beam delivery parameters, micro-dosimetric spectrum, and beam delivery parameters of conventional dose rate ion beams;

[0170] Based on the microdosimetric line energy spectrum of the ultra-high dose rate ion beam, the track-average line energy and dose-average line energy of the ultra-high dose rate ion beam are obtained.

[0171] Based on the beam delivery parameters of the ultra-high dose rate ion beam, the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation was obtained;

[0172] Survival curves of irradiated cells under normoxic and hypoxic conditions after conventional dose rate ion beam irradiation were obtained. The survival curves of irradiated cells under normoxic and hypoxic conditions were fitted using a linear quadratic (LQ) model to obtain the LQ model parameters under normoxic and hypoxic conditions. Radiation sensitivity parameters were determined based on the LQ model parameters under normoxic and hypoxic conditions using calibrated biological samples. Combined with the micro-dose line energy spectrum of the ultra-high dose rate ion beam and the instantaneous oxygen concentration of irradiated cells during ultra-high dose rate ion beam irradiation, the specific energy of the ultra-high dose rate ion beam radiation field in a specific cell region was obtained, as well as the oxygen increase ratio at which the ultra-high dose rate ion beam reached the specific biological effect endpoint under normoxic and hypoxic conditions.

[0173] Based on the linear square model parameters under normoxic and hypoxic conditions, the linear square model parameters for irradiated cells when the oxygen content in the cellular microenvironment tends to 0 and ∞ were obtained.

[0174] Based on the linear square model parameters of irradiated cells when the oxygen content in the cell microenvironment tends to 0 and ∞, the effect of any change in oxygen content in the cell microenvironment on the linear square model parameters of irradiated cells was obtained.

[0175] Based on the beam delivery parameters of ultra-high dose rate ion beams and conventional dose rate ion beams, and combined with the influence of changes in oxygen content in the arbitrary cellular microenvironment on the linear square model parameters of the irradiated cells, the FLASH protection effect factor (FSE) of ultra-high dose rate ion beams is obtained. This factor is used to iteratively optimize the irradiation scheme and obtain the final ultra-high dose rate ion beam radiation plan.

[0176] In another aspect, the present invention also provides a non-transitory computer-readable storage medium having a computer program stored thereon, which, when executed by a processor, implements the ultra-high dose rate ion beam radiation planning method based on microdosimetry provided by the methods described above, the method comprising:

[0177] To obtain the beam delivery parameters, micro-dosimetric spectrum, and beam delivery parameters of conventional dose rate ion beams;

[0178] Based on the microdosimetric line energy spectrum of the ultra-high dose rate ion beam, the track-average line energy and dose-average line energy of the ultra-high dose rate ion beam are obtained.

[0179] Based on the beam delivery parameters of the ultra-high dose rate ion beam, the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation was obtained;

[0180] Survival curves of irradiated cells under normoxic and hypoxic conditions after conventional dose rate ion beam irradiation were obtained. The survival curves of irradiated cells under normoxic and hypoxic conditions were fitted using a linear quadratic (LQ) model to obtain the LQ model parameters under normoxic and hypoxic conditions. Radiation sensitivity parameters were determined based on the LQ model parameters under normoxic and hypoxic conditions using calibrated biological samples. Combined with the micro-dose line energy spectrum of the ultra-high dose rate ion beam and the instantaneous oxygen concentration of irradiated cells during ultra-high dose rate ion beam irradiation, the specific energy of the ultra-high dose rate ion beam radiation field in a specific cell region was obtained, as well as the oxygen increase ratio at which the ultra-high dose rate ion beam reached the specific biological effect endpoint under normoxic and hypoxic conditions.

[0181] Based on the linear square model parameters under normoxic and hypoxic conditions, the linear square model parameters for irradiated cells when the oxygen content in the cellular microenvironment tends to 0 and ∞ were obtained.

[0182] Based on the linear square model parameters of irradiated cells when the oxygen content in the cell microenvironment tends to 0 and ∞, the effect of any change in oxygen content in the cell microenvironment on the linear square model parameters of irradiated cells was obtained.

[0183] Based on the beam delivery parameters of ultra-high dose rate ion beams and conventional dose rate ion beams, and combined with the influence of changes in oxygen content in the arbitrary cellular microenvironment on the linear square model parameters of the irradiated cells, the FLASH protection effect factor (FSE) of ultra-high dose rate ion beams is obtained. This factor is used to iteratively optimize the irradiation scheme and obtain the final ultra-high dose rate ion beam radiation plan.

[0184] The device embodiments described above are merely illustrative. The units described as separate components may or may not be physically separate. The components shown as units may or may not be physical units; that is, they may be located in one place or distributed across multiple network units. Some or all of the modules can be selected to achieve the purpose of this embodiment according to actual needs. Those skilled in the art can understand and implement this without any creative effort.

[0185] Through the above description of the embodiments, those skilled in the art can clearly understand that each embodiment can be implemented by means of software plus necessary general-purpose hardware platforms, and of course, it can also be implemented by hardware. Based on this understanding, the above technical solutions, in essence or the part that contributes to the prior art, can be embodied in the form of a software product. This computer software product can be stored in a computer-readable storage medium, such as ROM / RAM, magnetic disk, optical disk, etc., and includes several instructions to cause a computer device (which may be a personal computer, server, or network device, etc.) to execute the methods described in the various embodiments or some parts of the embodiments.

[0186] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for ultra-high dose rate ion beam radiation planning based on microdosimetry, characterized in that, include: To obtain the beam delivery parameters, micro-dosimetric spectrum, and beam delivery parameters of conventional dose rate ion beams; Based on the microdosimetric line energy spectrum of the ultra-high dose rate ion beam, the track-average line energy and dose-average line energy of the ultra-high dose rate ion beam are obtained. Based on the beam delivery parameters of the ultra-high dose rate ion beam, the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation was obtained; Survival curves of irradiated cells under normoxic and hypoxic conditions after conventional dose rate ion beam irradiation were obtained. Linear square model was used to fit these survival curves, yielding linear square model parameters under normoxic and hypoxic conditions. Radiation sensitivity parameters were determined based on calibrated biological samples using these linear square model parameters. Furthermore, the specific energy of the ultra-high dose rate ion beam radiation field in a specific cell region was obtained by combining the micro-dose line energy spectrum of the ultra-high dose rate ion beam and the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation. The oxygen increase ratio at which the ultra-high dose rate ion beam reached the specific biological effect endpoint under normoxic and hypoxic conditions was also determined. Based on the linear square model parameters under normoxic and hypoxic conditions, the oxygen content of irradiated cells in the cellular microenvironment tends to 0 and tends to... Parameters of the linear square model; Based on the oxygen content of irradiated cells in the cellular microenvironment tending towards 0 and oxygen content tending towards... The linear square model parameters were obtained to determine the effect of any change in oxygen content in the cellular microenvironment on the linear square model parameters of the irradiated cells. Based on the beam delivery parameters of ultra-high dose rate ion beams and conventional dose rate ion beams, and combined with the influence of changes in oxygen content in the arbitrary cell microenvironment on the linear square model parameters of the irradiated cells, the FLASH protection effect factor (FSE) of ultra-high dose rate ion beams is obtained. This factor is used to iteratively optimize the irradiation scheme and obtain the final ultra-high dose rate ion beam radiation plan. The process involves obtaining survival curves of irradiated cells under normoxic and hypoxic conditions after conventional dose-rate ion beam irradiation. These survival curves are then fitted using a linear square model to obtain linear square model parameters under normoxic and hypoxic conditions. Radiation sensitivity parameters are determined based on calibrated biological samples using these linear square model parameters. Furthermore, by combining the micro-dose line energy spectrum of the ultra-high dose-rate ion beam and the instantaneous oxygen concentration of the irradiated cells during ultra-high dose-rate ion beam irradiation, the specific energy of the ultra-high dose-rate ion beam radiation field in a specific cell region is obtained. Finally, the oxygen increase ratio at which the ultra-high dose-rate ion beam reaches a specific biological effect endpoint under normoxic and hypoxic conditions is also determined. Survival curves of cells in the normoxic and hypoxic groups irradiated with conventional dose-rate ion beams were obtained. The survival curves of the normoxic and hypoxic groups were then fitted using a linear quadratic (LQ) model to obtain the parameters of the LQ model under normoxic conditions. , Parameters of the linear square model under hypoxic conditions , ; Radiation sensitivity parameters were determined based on linear square model parameters under normoxic and hypoxic conditions from calibrated biological samples. , ,in, The radius of the radiation-sensitive microstructure region in the cell nucleus , The radius of the cell nucleus ; According to radiation sensitivity parameters By combining the micro-dosimetric spectrum of the ultra-high dose rate ion beam and using the first specific energy expression, the specific energy of the ultra-high dose rate ion beam radiation field in the radiation-sensitive microstructure region of the cell nucleus is obtained. According to radiation sensitivity parameters By combining the micro-dose line energy spectrum of the ultra-high dose rate ion beam and using the second specific energy expression, the specific energy of the ultra-high dose rate ion beam radiation field in the cell nucleus region is obtained. Based on the calibrated radiation biological effects, the radiation dose required to reach a specific radiation biological effect endpoint under normoxic and hypoxic conditions is determined respectively. Using the oxygen increase ratio expression, the oxygen increase ratio corresponding to the specific radiation biological effect endpoint is obtained. The first specific energy expression is: ， In the first specific energy expression This represents the specific energy of the ultra-high dose rate ion beam radiation field in the radiation-sensitive microstructure region of the cell nucleus. This represents the dose-average linear energy of an ultra-high dose rate ion beam. This represents the radius of the radiation-sensitive microstructure region in the cell nucleus. Indicates the density of irradiated cells, tissues, or materials. Represents pi; The expression for the second specific energy is: ， In the second specific energy expression, This represents the specific energy of the ultra-high dose rate ion beam radiation field in the cell nucleus region. Represents the radius of the cell nucleus. This represents the dose-average linear energy of an ultra-high dose rate ion beam. Indicates the radius of the cell nucleus region. Indicates the density of irradiated cells, tissues, or materials. Represents pi; The expression for the oxygen increase ratio is: ， In the oxygen increase ratio expression, This represents the oxygen gain ratio at which ultra-high dose rate ion beams reach specific radiation biological effect endpoints under both normoxic and hypoxic conditions. This represents the ultra-high dose rate ion beam radiation dose required to reach a specific radiation biological effect endpoint under hypoxic conditions. This refers to the ultra-high dose rate ion beam radiation dose required to reach a specific radiation biological effect endpoint under normal oxygen conditions.

2. The ultra-high dose rate ion beam radiation planning method based on microdosimetry according to claim 1, characterized in that, The process of obtaining the track-average linear energy and dose-average linear energy of an ultra-high dose rate ion beam based on its micro-dosage linear energy spectrum includes: Based on the microdosimetric line energy spectrum of ultra-high dose rate ion beams, the track-average line energy of ultra-high dose rate ion beams is obtained using the expression for track-average line energy. Based on the microdosimetric line energy spectrum of ultra-high dose rate ion beams, the dose-average line energy of ultra-high dose rate ion beams is obtained using the expression for dose-average line energy. The expression for the track-average linear energy is: ， In the expression for the linear energy of the track average, This represents the average linear energy of the trajectory of an ultra-high dose rate ion beam. This represents the line energy of an ultra-high dose rate ion beam in the micro-dose line energy spectrum. This represents the probability density of ultra-high dose rate ion beams in the micro-dose line energy spectrum; The expression for the dose-average linear energy is as follows: ， In the expression for dose-average linear energy, This represents the dose-average linear energy of an ultra-high dose rate ion beam. This represents the average linear energy of the trajectory of an ultra-high dose rate ion beam. This represents the line energy of an ultra-high dose rate ion beam in the micro-dose line energy spectrum. This represents the probability density of ultra-high dose rate ion beams in the micro-dose line energy spectrum.

3. The ultra-high dose rate ion beam radiation planning method based on microdosimetry according to claim 2, characterized in that, The method of obtaining the instantaneous oxygen concentration of irradiated cells during ultra-high dose rate ion beam irradiation based on the beam delivery parameters of the ultra-high dose rate ion beam includes: Based on the beam delivery parameters of the ultra-high dose rate ion beam, the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation is obtained using the oxygen concentration expression, where the oxygen concentration expression is: ， = ， In the oxygen concentration expression, This indicates the change in instantaneous oxygen concentration of irradiated cells over time during ultra-high dose rate ion beam irradiation. Indicates the ambient oxygen concentration. This indicates the rate at which the intracellular environment of the irradiated cell obtains oxygen from the external environment. Indicates time, This indicates the instantaneous dose rate of an ultra-high dose rate ion beam. γ represents the rate constant of radiative oxygen depletion, and γ represents the rate constant based on the instantaneous dose rate. The rate at which the intracellular environment of an irradiated cell obtains oxygen from the external environment. and the rate constant of radiation oxygen depletion The obtained parameters show the changes in cellular oxygen content.

4. The ultra-high dose rate ion beam radiation planning method based on microdosimetry according to claim 3, characterized in that, Based on the linear square model parameters for normoxic and hypoxic conditions under conventional dose rate irradiation, it was found that the oxygen content in the cellular microenvironment of irradiated cells tends to 0 and the oxygen content tends to 1 under conventional dose rate irradiation. The parameters of the linear squared model include: Based on the linear square model parameters under normal dose rate irradiation conditions and normoxic conditions , Parameters of the linear square model under hypoxic conditions , The linear square model parameters were obtained for irradiated cells in the cellular microenvironment where the oxygen content tends to 0. , The oxygen content of irradiated cells in the cellular microenvironment tends to be... Linear square model parameters , ; Based on the squared model parameters of the oxygen content in the irradiated cells' cellular microenvironment tending towards 0. , The oxygen content of irradiated cells in the cellular microenvironment tends to be... Square model parameters , Based on the specific energy of the ultra-high dose rate ion beam radiation field in the radiation-sensitive microstructure region of the cell nucleus and the specific energy of the ultra-high dose rate ion beam radiation field in the cell nucleus region, linear square model parameters were obtained for cells irradiated with ion beams of corresponding radiation quality where the oxygen content in the cellular microenvironment tends to zero. , Parameters of the linear square model with oxygen content approaching infinity , .

5. The ultra-high dose rate ion beam radiation planning method based on microdosimetry according to claim 4, characterized in that, Based on the squared model parameters of the oxygen content in the irradiated cells' cellular microenvironment tending towards 0. , The oxygen content of irradiated cells in the cellular microenvironment tends to be... Square model parameters , And using the specific energy of the ultra-high dose rate ion beam radiation field in the radiation-sensitive microstructure region of the cell nucleus and the specific energy of the ultra-high dose rate ion beam radiation field in the cell nucleus region, the linear square model parameters for a cell irradiated with an ion beam of corresponding radiation quality tending towards 0 in the cellular microenvironment are obtained using the first transformation equation. , Parameters of the linear square model with oxygen content approaching infinity , The first transformation is: ， ， ， ， In the first transformation, , The parameters represent the linear squared model parameters for cells irradiated by ion beams of corresponding radiation qualities, where the oxygen content in the cellular microenvironment tends to zero. , The parameters represent the linear square model parameters for cells irradiated by ion beams of corresponding radiation qualities, where the oxygen content in the cellular microenvironment tends to infinity. This represents the specific energy of the ultra-high dose rate ion beam radiation field in the radiation-sensitive microstructure region of the cell nucleus. This represents the specific energy of the ultra-high dose rate ion beam radiation field in the cell nucleus region. , These represent the squared model parameters for the oxygen content of irradiated cells in the cellular microenvironment tending towards 0. , These represent the oxygen content of irradiated cells tending towards a certain level in the cellular microenvironment. The squared model parameters.

6. The ultra-high dose rate ion beam radiation planning method based on microdosimetry according to claim 5, characterized in that, The statement is based on the fact that the oxygen content of the irradiated cells in the cellular microenvironment tends to be 0 and the oxygen content tends to be... The linear square model parameters were obtained to determine the effect of any change in oxygen content in the cellular microenvironment on the linear square model parameters, including: Based on the linear square model parameters of cells irradiated with ion beams of corresponding radiation quality, the oxygen content in the cellular microenvironment tends to zero. The parameters of a linear square model for cells irradiated with ion beams of corresponding radiation quality in their cellular microenvironment where oxygen content tends to infinity. Using the first impact expression, the first impact factor is obtained; Based on the linear square model parameters of cells irradiated with ion beams of corresponding radiation quality, the oxygen content in the cellular microenvironment tends to zero. The parameters of a linear square model for cells irradiated with ion beams of corresponding radiation quality in their cellular microenvironment where oxygen content tends to infinity. Using the second influence expression, the second influence factor is obtained; The expression for the first influence is: ， The second influence expression is: ， In the formula, Indicates the first impact factor. This indicates the second impact factor. Indicates the partial pressure of oxygen. This indicates the oxygen concentration at the midpoint of the corresponding oxygen increase ratio curve. , The parameters represent the linear squared model parameters for cells irradiated by ion beams of corresponding radiation qualities, where the oxygen content in the cellular microenvironment tends to zero. , These represent the linear square model parameters for cells irradiated by ion beams of corresponding radiation quality, where the oxygen content in the cellular microenvironment tends to infinity.

7. The ultra-high dose rate ion beam radiation planning method based on microdosimetry according to claim 6, characterized in that, The process involves using the beam delivery parameters of ultra-high dose rate ion beams and conventional dose rate ion beams, combined with the influence of arbitrary changes in oxygen content in the cellular microenvironment on the parameters of the cell linear square model, to obtain the irradiation scheme FSE for ultra-high dose rate ion beams. This scheme is then used to iteratively optimize the irradiation scheme and obtain the final ultra-high dose rate ion beam radiation plan, including: Based on the beam delivery parameters of ultra-high dose rate ion beams and conventional dose rate ion beams, and considering the influence of arbitrary changes in oxygen content in the cellular microenvironment on the linear square model parameters of cells, the linear square model parameters for ultra-high dose rate ion beam irradiation were obtained. , Linear square model parameters for conventional dose rate ion beam irradiation , ; Based on the linear square model parameters of ultra-high dose rate ion beam irradiation , Linear square model parameters for conventional dose rate ion beam irradiation , The irradiation scheme FSE of the ultra-high dose rate ion beam is obtained, which is used to iteratively optimize the irradiation scheme and obtain the final ultra-high dose rate ion beam radiation plan.

8. The ultra-high dose rate ion beam radiation planning method based on microdosimetry according to claim 7, characterized in that, Based on the beam delivery parameters of ultra-high dose rate ion beams and conventional dose rate ion beams, and considering the influence of arbitrary changes in oxygen content in the cellular microenvironment on the parameters of the linear square model of cells, the parameters of the linear square model of ultra-high dose rate ion beam irradiation are obtained using the second transformation equation. , Linear square model parameters for conventional dose rate ion beam irradiation , The second transformation is: ， ， In the second transformation, This represents the change in instantaneous oxygen concentration of irradiated cells with time t during ultra-high dose rate ion beam irradiation, where T represents the total irradiation time. When... Instantaneous dose rate When the dose rate is within the conventional range, the calculation result is the linear square model parameter for conventional dose rate ion beam irradiation. , ,when Instantaneous dose rate When the FLASH ultra-high dose rate range is reached, the calculation results are the linear square model parameters for ultra-high dose rate ion beam irradiation. , , This represents the first influencing factor when the instantaneous oxygen concentration is O. This represents the second influencing factor when the instantaneous oxygen concentration is O. This indicates the oxygen concentration at the midpoint of the corresponding oxygen increase ratio curve. This indicates integration over the time variable t.

9. The ultra-high dose rate ion beam radiation planning method based on microdosimetry according to claim 8, characterized in that, Based on the linear square model parameters of ultra-high dose rate ion beam irradiation , Linear square model parameters for conventional dose rate ion beam irradiation , Using the FSE expression, the irradiation scheme FSE for ultra-high dose rate ion beams is obtained, which is used to iteratively optimize the irradiation scheme and obtain the final ultra-high dose rate ion beam radiation plan. The FSE expression is: ， In the FSE expression, , These represent the linear square model parameters corresponding to the ultra-high dose rate ion beam irradiation scheme; , ... and These represent the ultra-high dose rate FLASH ion beam radiation dose and the conventional dose rate ion beam radiation dose required to achieve the same radiation biological effect, respectively.

10. A high dose rate ion beam radiation planning system based on microdosimetry, characterized in that, include: The data acquisition module is used to acquire the beam delivery parameters of ultra-high dose rate ion beams, micro-dosimetry line energy spectra, and beam delivery parameters of conventional dose rate ion beams. The first processing module is used to: obtain the track-average linear energy and dose-average linear energy of the ultra-high dose rate ion beam based on the microdosimetric linear energy spectrum of the ultra-high dose rate ion beam. The second processing module is used to: obtain the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation based on the beam delivery parameters of the ultra-high dose rate ion beam; The third processing module is used to: obtain the survival curves of normoxic and hypoxic cells irradiated by conventional dose rate ion beams; fit the survival curves of normoxic and hypoxic cells using a linear square (LQ) model to obtain the LQ model parameters under normoxic and hypoxic conditions; determine the radiation sensitivity parameters based on the LQ model parameters under normoxic and hypoxic conditions using calibrated biological samples; and, combined with the micro-dose line energy spectrum of the ultra-high dose rate ion beam and the instantaneous oxygen concentration of the irradiated cells during ultra-high dose rate ion beam irradiation, obtain the specific energy of the ultra-high dose rate ion beam radiation field in a specific cell region, and obtain the oxygen increase ratio at which the ultra-high dose rate ion beam reaches the specific biological effect endpoint under normoxic and hypoxic conditions. The fourth processing module is used to: obtain the oxygen content of irradiated cells tending towards 0 and the oxygen content tending towards 0 in the cellular microenvironment, based on the linear square model parameters under normoxic and hypoxic conditions. Parameters of the linear square model; The fifth processing module is used to: determine whether the oxygen content of the irradiated cells in the cellular microenvironment tends to 0 or to a certain value. The linear square model parameters were obtained to determine the effect of any change in oxygen content in the cellular microenvironment on the linear square model parameters of the irradiated cells. The planning module is used to: obtain the FLASH protection effect factor (FSE) of the ultra-high dose rate ion beam based on the beam delivery parameters of the ultra-high dose rate ion beam and the conventional dose rate ion beam, combined with the influence of changes in oxygen content in the cell microenvironment on the linear square model parameters of the irradiated cells, and to iteratively optimize the irradiation scheme and obtain the final ultra-high dose rate ion beam radiation plan. The process involves obtaining survival curves of irradiated cells under normoxic and hypoxic conditions after conventional dose-rate ion beam irradiation. These survival curves are then fitted using a linear square model to obtain linear square model parameters under normoxic and hypoxic conditions. Radiation sensitivity parameters are determined based on calibrated biological samples using these linear square model parameters. Furthermore, by combining the micro-dose line energy spectrum of the ultra-high dose-rate ion beam and the instantaneous oxygen concentration of the irradiated cells during ultra-high dose-rate ion beam irradiation, the specific energy of the ultra-high dose-rate ion beam radiation field in a specific cell region is obtained. Finally, the oxygen increase ratio at which the ultra-high dose-rate ion beam reaches a specific biological effect endpoint under normoxic and hypoxic conditions is also determined. Survival curves of cells in the normoxic and hypoxic groups irradiated with conventional dose-rate ion beams were obtained. The survival curves of the normoxic and hypoxic groups were then fitted using a linear quadratic (LQ) model to obtain the parameters of the LQ model under normoxic conditions. , Parameters of the linear square model under hypoxic conditions , ; Radiation sensitivity parameters were determined based on linear square model parameters under normoxic and hypoxic conditions from calibrated biological samples. , ,in, The radius of the radiation-sensitive microstructure region in the cell nucleus , The radius of the cell nucleus ; According to radiation sensitivity parameters By combining the micro-dosimetric spectrum of the ultra-high dose rate ion beam and using the first specific energy expression, the specific energy of the ultra-high dose rate ion beam radiation field in the radiation-sensitive microstructure region of the cell nucleus is obtained. According to radiation sensitivity parameters By combining the micro-dose line energy spectrum of the ultra-high dose rate ion beam and using the second specific energy expression, the specific energy of the ultra-high dose rate ion beam radiation field in the cell nucleus region is obtained. Based on the calibrated radiation biological effects, the radiation dose required to reach a specific radiation biological effect endpoint under normoxic and hypoxic conditions is determined respectively. Using the oxygen increase ratio expression, the oxygen increase ratio corresponding to the specific radiation biological effect endpoint is obtained. The first specific energy expression is: ， In the first specific energy expression This represents the specific energy of the ultra-high dose rate ion beam radiation field in the radiation-sensitive microstructure region of the cell nucleus. This represents the dose-average linear energy of an ultra-high dose rate ion beam. This represents the radius of the radiation-sensitive microstructure region in the cell nucleus. Indicates the density of irradiated cells, tissues, or materials. Represents pi; The expression for the second specific energy is: ， In the second specific energy expression, This represents the specific energy of the ultra-high dose rate ion beam radiation field in the cell nucleus region. Represents the radius of the cell nucleus. This represents the dose-average linear energy of an ultra-high dose rate ion beam. Indicates the radius of the cell nucleus region. Indicates the density of irradiated cells, tissues, or materials. Represents pi; The expression for the oxygen increase ratio is: ， In the oxygen increase ratio expression, This represents the oxygen gain ratio at which ultra-high dose rate ion beams reach specific radiation biological effect endpoints under both normoxic and hypoxic conditions. This represents the ultra-high dose rate ion beam radiation dose required to reach a specific radiation biological effect endpoint under hypoxic conditions. This refers to the ultra-high dose rate ion beam radiation dose required to reach a specific radiation biological effect endpoint under normal oxygen conditions.

11. An electronic device comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, characterized in that, When the processor executes the program, it implements the ultra-high dose rate ion beam radiation planning method based on microdosimetry as described in any one of claims 1 to 9.

12. A non-transitory computer-readable storage medium having a computer program stored thereon, characterized in that, When the computer program is executed by the processor, it implements the ultra-high dose rate ion beam radiation planning method based on microdosimetry as described in any one of claims 1 to 9.

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