Small animal proton mini-beam irradiation system and method based on 3D printing collimator

Abstract

The invention discloses a small animal proton mini-beam irradiation system and method based on a 3D printing collimator, and the system comprises a supporting mechanism which comprises a supporting pedestal and a supporting backboard extending upwards from the supporting pedestal; the positioning mechanism comprises a bearing platform and a lifting driving assembly; the collimator assembly is arranged on the bearing platform and is provided with a beam outlet surface facing the supporting base; the lifting driving assembly drives the bearing platform to do lifting motion so as to drive the beam outlet surface of the collimator assembly to actively approach or fit the surface of the target area of the small animal to be irradiated; the verification control module is configured to perform Monte Carlo dose simulation based on the individualized image data of the small animal to be irradiated in combination with the physical model of the collimator assembly to generate predicted dose distribution; and the accuracy of dose delivery is verified by comparing the actually measured dose distribution obtained by using the collimator assembly with the predicted dose distribution. And a reliable, accurate and repeatable technical means is provided for proton mini-beam research.

Description

Technical Field

[0001] This invention relates to the field of precision radiotherapy experimental technology, and in particular to a small animal proton mini-beam irradiation system and method based on a 3D-printed collimator. Background Technology

[0002] In recent years, proton mini-beam radiotherapy (pMBRT) has emerged as a novel spatial fractionation radiotherapy technique. This technique utilizes submillimeter-scale microbeam arrays to generate extremely high peak-to-valley dose ratios (PVDR), effectively killing tumors while protecting normal tissues, and has enormous potential for clinical translation.

[0003] To delve deeper into the biological mechanisms of pMBRT, optimize treatment parameters, and promote its clinical translation, systematic irradiation experiments using small animal models are needed in the preclinical research phase. However, many gaps and challenges remain in this experimental technology field, and a mature, standardized, and fully controllable experimental system and methodology have not yet been established. Specifically, existing technologies mainly face the following problems: First, in terms of hardware, there is a lack of standardized, high-precision collimators specifically designed for small animal pMBRT experiments. Traditional machining or assembly-type collimators are difficult to manufacture economically and quickly with complex internal microchannel structures and sub-millimeter precision. Their geometric accuracy and consistency often cannot meet the stringent requirements of microbeam arrays for dose distribution. At the same time, existing experimental devices usually lack dedicated positioning platforms that can be easily integrated with proton therapy equipment and achieve precise target localization and fixation in small animals.

[0004] Secondly, regarding dose prediction and validation, a closed-loop quality assurance process covering simulation, validation, and implementation has not yet been established for individualized small animal models. Small animals are small in size, have complex anatomical structures, and exhibit differences between individuals. General dose calculation models often fail to accurately predict the actual dose distribution of microbeams within biological tissues. The lack of a direct comparison between detailed Monte Carlo simulations based on individual CT images and high-resolution physical dose validation makes it difficult to ensure consistency between the planned treatment dose and the actual irradiation dose, thus affecting the reliability and reproducibility of experimental results.

[0005] Furthermore, precisely controlling the "skin gap" (i.e., the air gap between the collimator exit surface and the animal's skin / target area surface) along the beam path is a major challenge during irradiation. This air gap causes multiple Coulomb scattering of the proton beam in the air, increasing the full width at half maximum (FWHM) of the microbeam, disrupting the expected sharp dose peak, and reducing PVDR, thus affecting the assessment of the experimental biological effects. Existing methods generally struggle to achieve and maintain stable zero-gap or minimal-gap conditions during live animal irradiation.

[0006] In summary, there is an urgent need for a systematic solution that integrates high-precision collimator manufacturing, individualized dose prediction and verification, and precise near-field irradiation positioning to fill the gap in dedicated experimental equipment and standardized methods in this field, and to provide reliable, accurate and reproducible technical support for biological research on pMBRT. Summary of the Invention

[0007] In a first aspect, to address the aforementioned technical problems, a small animal proton mini-beam irradiation system based on a 3D-printed collimator is provided, comprising: The support mechanism includes a support base for supporting and securing the small animal to be irradiated, and a support back plate extending upward from the support base; The positioning mechanism includes a support platform disposed on the support back plate and a lifting drive assembly for driving the support platform to rise and fall. A collimator assembly, detachably mounted on the support platform, has a beam exit surface facing the support base. The beam exit surface spatially divides the vertically incident proton beam to form a micro-beam array. A lifting drive assembly drives the support platform to move up and down, causing the beam exit surface of the collimator assembly to actively approach or conform to the surface of the target area of ​​the small animal to be irradiated. The verification control module is configured to perform Monte Carlo dose simulation based on the individualized image data of the animal to be irradiated and the physical model of the collimator assembly to generate a predicted dose distribution; and to verify the accuracy of dose delivery by comparing the measured dose distribution obtained using the collimator assembly with the predicted dose distribution.

[0008] Furthermore, the collimator assembly is a structural component integrally formed by additive manufacturing technology, and its interior has multiple parallel and penetrating micro-beam channels.

[0009] Furthermore, the additive manufacturing technology is photopolymerization molding technology, and the material of the collimator assembly is a photopolymerized resin composite material.

[0010] Furthermore, the cross-sectional width of the microbeam channel is 0.4 mm to 1.0 mm, and the center distance between adjacent channels is 1.0 mm to 3.0 mm.

[0011] Furthermore, the collimator assembly includes a horizontal portion and a vertical portion: The horizontal part is embedded in the bearing platform, and a limiting through hole that matches the beam exit surface is provided at the center of the horizontal part; The interior of the vertical section is equipped with a micro-pore array that spatially divides the incident proton beam, and one end of the vertical section is embedded in the limiting through hole and directly faces the small animal to be irradiated on the support base.

[0012] Preferably, the collimator assembly has an inverted T-shaped structure.

[0013] Furthermore, the collimator assembly has a visual alignment mark on its top or outer side for use in conjunction with an external laser positioning system to align the beam channel with the target area.

[0014] Furthermore, the lifting drive assembly includes a Z-axis lifting screw, an adjusting handwheel that cooperates with the Z-axis lifting screw, and a guide rod for guiding the direction of movement.

[0015] Furthermore, the verification control module includes: The image processing unit is used to import and process CT images of the object to be irradiated; A Monte Carlo dose engine is used to load the digital model and material parameters of the collimator assembly and calculate the predicted dose distribution. The film dose analysis unit is used to analyze the dose image obtained after irradiation of radiochromic film, obtain the measured dose distribution, and perform Gamma pass rate analysis on the measured dose distribution and the predicted dose distribution.

[0016] A second aspect of the present invention provides a method for proton mini-beam irradiation of small animals based on a 3D-printed collimator using the system, comprising the following steps: Providing a collimator: Providing a collimator assembly with predetermined microbeam channel parameters; Dose prediction steps: Acquire target area images of the small animal to be irradiated, and perform Monte Carlo simulation based on the images and collimator components to obtain the predicted dose distribution within the target area; Dosage verification steps: Pre-irradiate the dose measurement device using a collimator assembly to obtain the measured dose distribution, and determine whether the consistency between the measured dose distribution and the predicted dose distribution meets a preset standard; Positioning and irradiation steps: If the preset standard is met, fix the small animal to the support base, adjust the position of the carrier platform to align the target area with the collimator assembly, and move the carrier platform so that the beam exit surface is in contact with the surface of the small animal target area or reaches a preset small distance, and then perform proton beam irradiation.

[0017] Furthermore, in the dose verification step, if the consistency does not meet the preset standard, the material parameters in the Monte Carlo simulation are adjusted or the collimator assembly is re-fabricated, and the dose prediction step and the dose verification step are re-executed.

[0018] Furthermore, in the positioning irradiation step, the driving support platform is raised and lowered so that the beam exit surface of the collimator assembly moves towards the small animal, and the beam exit surface is used to flatten the natural bulge of the target area surface to form a flat interface suitable for microbeam array incident.

[0019] Compared with the prior art, the embodiments of the present invention have the following beneficial effects: This invention introduces an independently installable modular system that combines a 3D-printed high-precision collimator, an actively fitted support platform, and a personalized end-to-end verification and control module. This creates a standardized and reusable experimental platform that ensures the geometric precision and dose delivery accuracy of sub-millimeter-scale microbeams within complex biological systems. The active fitting mechanism physically eliminates beam gaps and suppresses scattering, while the personalized simulation-verification-implementation process guarantees dose consistency from prediction to actual irradiation. This provides a reliable, precise, and repeatable technical means for studying the biological effects of proton mini-beams, filling a gap in dedicated experimental systems and methods in this field. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1 This is a system flowchart disclosed in this invention; Figure 2 This is a schematic diagram of the overall structure disclosed in this invention.

[0022] In the picture: 110. Support base; 120. Support back plate; 130. Reinforcing support component; 210. Load-bearing platform; 221. Z-axis lifting screw; 222. Adjusting handwheel; 223. Guide rod; 300. Collimator assembly. Detailed Implementation

[0023] To enable those skilled in the art to better understand the present invention, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0024] The present invention aims to provide a small animal proton mini-beam irradiation system based on a 3D-printed collimator. This system is a stand-alone device that can be placed as a whole on the treatment bed of a proton therapy machine or a dedicated experimental platform. As an additional experimental device, it does not depend on or require any structural modification to the existing proton therapy machine head.

[0025] The system mainly consists of four parts: a support mechanism, a positioning mechanism, a 3D printed collimator assembly, and an individualized verification control module. These are described in detail below.

[0026] First, the supporting institutions will be explained in detail.

[0027] The support mechanism constitutes the mechanical foundation framework of the entire system. It is a frame structure with a stable base, which can be placed independently and stably on the treatment bed or dedicated experimental platform of the proton therapy machine. The support mechanism mainly includes a support base 110, a support back plate 120, and reinforcing support components 130.

[0028] The support base 110 serves as the system base, used to securely place the device on the treatment bed or table. The upper surface of the support base 110 is directly used to support and fix the small animal to be irradiated (not shown in the figure, for example, an anesthetized mouse is fixed here by tape or a fitting mold).

[0029] The support backplate 120 extends vertically upward from the rear side of the support base 110, providing a mounting base for the positioning mechanism and collimator assembly.

[0030] The reinforcing support 130 is connected between the support base 110 and the support back plate 120. It is usually in the form of a triangular or diagonal brace structure, used to enhance the rigidity of the support back plate 120 and ensure the overall stability of the system during load-bearing and movement.

[0031] Then, the positioning mechanism will be described in detail.

[0032] The positioning mechanism is used to achieve precise movement of the collimator assembly 300 in the vertical direction (Z-axis) to realize the active fitting function. It mainly includes the support platform 210 and the lifting drive assembly.

[0033] The support platform 210 is located on the front of the support back plate 120 and has an outwardly extending cantilever structure. A through hole is provided in the central area of ​​the support platform 210. The size of the through hole matches the beam output surface of the collimator assembly 300, so that after the collimator is installed, its beam output surface can directly face the support base 110 below through this hole.

[0034] The lifting drive assembly is used to drive the support platform 210 to perform high-precision lifting and lowering movements along the support back plate 120. In a preferred embodiment, the lifting drive assembly includes a Z-axis lifting screw 221, an adjusting handwheel 222 that cooperates with the Z-axis lifting screw 221, and a guide rod 223 for guiding the direction of movement. The Z-axis lifting screw 221 is vertically mounted, and its rotational motion is converted into linear lifting and lowering motion of the support platform 210 through a threaded joint. The adjusting handwheel 222 is connected to the end of the Z-axis lifting screw 221, allowing the operator to manually rotate it to achieve fine-tuning control of the height of the support platform 210. The guide rod 223 is arranged parallel to the Z-axis lifting screw 221 and cooperates with a linear bearing on the support platform 210 to constrain the direction of movement of the support platform 210, preventing its rotation and ensuring smooth and precise lifting.

[0035] Next, the alignment assembly 300 will be described in detail.

[0036] The collimator assembly 300 is the core functional component for generating the microbeam array, and it is detachably mounted within a recess in the support platform 210. The collimator assembly 300 has an exit surface facing the support base 110, which spatially divides the vertically incident proton beam to form the microbeam array. A lifting drive assembly drives the support platform 210 to move up and down, causing the exit surface of the collimator assembly 300 to actively approach or conform to the surface of the target area of ​​the small animal to be irradiated.

[0037] In one specific embodiment, the collimator assembly 300 has an inverted T-shaped structure, consisting of a horizontal part and a vertical part. The horizontal part is embedded or fixed on the support platform 210, and a limiting through hole is provided at its center, which is aligned with the through hole of the support platform 210. The vertical part is the main functional part, and its upper end is internally arranged with multiple parallel and through micro-beam channels, forming a micro-pore array; the lower end of the vertical part is embedded in the limiting through hole of the horizontal part and extends downward, so that the bottom surface (i.e., the beam exit surface) of the lower end of the vertical part can pass through the support platform 210 and protrude from the lower surface of the support platform 210, thereby facing the animal target area on the support base 110 below without obstruction, achieving close-range / close-fitting irradiation.

[0038] In this design, the collimator assembly is a one-piece structural component manufactured using additive manufacturing technology to ensure the geometric accuracy and consistency of the sub-millimeter-level microchannels. It contains multiple parallel and interconnected microbeam channels. Specifically, the additive manufacturing technology is photopolymerization molding, and the collimator assembly is made of photopolymerized resin composite material. The cross-sectional width of the microbeam channels ranges from 0.4 mm to 1.0 mm, and the center-to-center distance between adjacent channels ranges from 1.0 mm to 3.0 mm to meet the peak-to-valley dose ratio (PVDR) requirements for small animal experiments.

[0039] Visual alignment marks (crosshairs) can be set on the top or outside of the collimator assembly 300 to work with an external laser positioning system to achieve precise alignment of the beam channel with the animal target area.

[0040] Finally, the verification control module is described in detail.

[0041] The verification control module is the software and control core of the system, implemented by a general-purpose computer equipped with dedicated software. It is configured to perform Monte Carlo dose simulation based on individualized image data of the object to be irradiated, combined with the physical model of the collimator assembly, to generate a predicted dose distribution; and to verify the accuracy of dose delivery by comparing the measured dose distribution obtained using the collimator assembly with the predicted dose distribution.

[0042] In a further embodiment, the verification control module includes an image processing unit, a Monte Carlo dosimetry engine, and a film dosimetry analysis unit. The image processing unit imports and processes CT images of the small animal to be irradiated; the Monte Carlo dosimetry engine loads the digital model and material parameters of the collimator assembly and calculates the predicted dose distribution; the film dosimetry analysis unit analyzes the dose image obtained after irradiation of the radiochromic film, obtains the measured dose distribution, and performs Gamma pass rate analysis on the measured and predicted dose distributions.

[0043] The Monte Carlo dosing engine integrates the core calculation modules of Monte Carlo simulation software such as TOPAS and GATE. It can load precise 3D digital models (STL format) of 3D-printed collimator components and assign them material properties based on pre-stored or user-inputted physical property tables of photocurable resin composite materials (including density, elemental composition, electron density, etc.). Based on imported CT images and set beam parameters (energy, dose, field, etc.), the Monte Carlo dosing engine simulates and calculates the 3D dose distribution of the proton microbeam after passing through the collimator within the biological body, generating a predicted dose map and calculating key indicators such as peak-to-valley dose ratio (PVDR).

[0044] The film dose analysis unit processes scanned images from radiochromic films such as EBT3. This unit converts the film's optical density values ​​into absorbed dose values ​​using a calibration curve, generating a two-dimensional measured dose distribution map. Subsequently, this unit performs a gamma consistency analysis between the measured dose distribution and the predicted dose distribution obtained from the Monte Carlo dosimetry engine under the same geometric conditions, and outputs the pass rate.

[0045] Based on the above system, the present invention also provides a method for proton mini-beam irradiation of small animals based on a 3D-printed collimator, such as... Figure 1 As shown, it mainly includes the following steps: S1. Providing a collimator: Providing a collimator assembly with predetermined microbeam channel parameters; S2. Dose prediction step: Obtain the target area image of the small animal to be irradiated, and perform Monte Carlo simulation based on the target area image and collimator assembly to obtain the predicted dose distribution in the target area. S3. Dose verification step: Pre-irradiate the dose measurement device using the collimator assembly to obtain the measured dose distribution, and determine whether the consistency between the measured dose distribution and the predicted dose distribution meets the preset standard. S4. Positioning Irradiation Steps: If the preset standards are met, fix the small animal on the support base 110, adjust the position of the carrier platform 210 to align the target area with the collimator assembly 300, and move the carrier platform 210 so that the beam exit surface is in contact with the surface of the small animal target area or reaches a preset small distance, and then perform proton beam irradiation.

[0046] In a further proposed approach, if the consistency does not meet the preset standard during the dose verification step, the material parameters in the Monte Carlo simulation are adjusted or the collimator assembly is re-fabricated, and the dose prediction and dose verification steps are re-executed.

[0047] Taking the proton mini-beam irradiation of subcutaneous xenografts in C57BL / 6 mice as an example, the specific implementation steps are as follows: S1, Digital Additive Manufacturing Collimator Based on the experimental design, the microbeam parameters were determined (e.g., beam half-width at half-maximum 0.5 mm, center-to-center distance 1.5 mm). A corresponding inverted T-shaped collimator digital model was designed using 3D modeling software, with the thickness of the microbeam generating section determined based on proton energy calculations. After slicing the model, it was printed using a specific formulation of photocurable resin via an SLA 3D printer. Following printing, thorough UV post-curing and ultrasonic cleaning were performed to ensure a smooth, residue-free channel interior.

[0048] S2, Monte Carlo Dose Prediction A C57BL / 6 mouse with a right hind limb dorsal fossa inoculated with Lewis lung cancer cells (LLC) and a tumor diameter of approximately 8 mm was selected. After anesthetizing the mouse, it was placed prone in a phantom for localization CT (Micro-CT) scanning. The CT data was imported into the Monte Carlo (TOPAS) dosimetry engine. The digital model of the collimator from step S1 was loaded into the engine, and the material density and elemental composition parameters corresponding to the resin grade were retrieved from the built-in database. In the simulation settings, the lower surface of the collimator microbeam generation section (i.e., the beam exit surface) was set to zero-distance contact with the tumor surface outlined in the CT image. Parameters such as proton beam energy and total monitoring units (MU) were set, and the simulation was run to obtain the three-dimensional dose distribution of the tumor and surrounding tissues. The PVDR of the tumor region was evaluated and confirmed to be greater than 10; otherwise, the microbeam parameters or collimator design were adjusted.

[0049] S3, Physical Dosimetry Verification Before formal irradiation, an EBT3 radiochromic film is placed on the surface of a solid water phantom; this position simulates the incidence depth of a mouse tumor. The 3D-printed collimator entity prepared in step S1 is mounted on the support platform 210 and placed under the proton therapy beam. The support platform 210 is adjusted to ensure the lower surface of the collimator is in close contact with the film surface. A proton beam irradiation is performed according to the MU settings used in the simulation in step S2. The film is then removed, allowed to stand, and scanned. The measured two-dimensional dose distribution is obtained using the film dose analysis unit. Gamma analysis is performed on this measured distribution and the predicted dose distribution extracted by the Monte Carlo engine on the same plane (the surface of the water phantom). If the pass rate is ≥96.5%, the verification is successful, and the collimator entity and simulation parameters are reliable. If the verification fails, the material density parameters in the Monte Carlo model need to be checked and corrected, or the collimator printing may be defective; reprinting and verification are then performed.

[0050] S4, Close-Contact Irradiation Coarse localization: The anesthetized tumor-bearing mouse is placed prone in a U-shaped limiting mold, with the tumor naturally bulging upwards and exposed at the U-shaped opening.

[0051] Laser Alignment (X / Y Axis): Activate the laboratory green crosshair laser and move the entire straddle support assembly horizontally (or adjust the treatment bed) to precisely align the laser crosshair center with the geometric center of the mouse subcutaneous tumor. Simultaneously, observe and fine-tune the collimator angle to ensure that the laser positioning aid marks on its surface (the "crosshair") coincide with the laser line, thereby ensuring that the microbeam array orientation is consistent with the experimental design requirements.

[0052] Active contact and flattening (Z-axis): The operator slowly rotates the adjusting handwheel 222, and the Z-axis lifting screw 221, guided by the guide rod 223, drives the support platform 210 and the collimator assembly 300 on it to descend smoothly. The descent stops when the output surface of the collimator assembly 300 contacts and slightly flattens the natural bulge on the surface of the animal target area. At this point, zero-air-gap physical contact is achieved, accurately replicating the boundary conditions during dose simulation.

[0053] Irradiation: After confirming that all positioning is correct, start the proton therapy machine and perform a single high-dose irradiation according to the verified MU parameters.

[0054] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A small animal proton mini-beam irradiation system based on a 3D-printed collimator, characterized in that, include: The support mechanism includes a support base (110) for supporting and fixing the small animal to be irradiated, and a support back plate (120) extending upward from the support base (110). The positioning mechanism includes a support platform (210) disposed on the support back plate (120) and a lifting drive assembly for driving the support platform (210) to rise and fall; A collimator assembly (300) is detachably mounted on the support platform (210). The collimator assembly (300) has a beam exit surface facing the support base (110). The beam exit surface spatially divides the vertically incident proton beam to form a micro-beam array. The lifting drive assembly drives the support platform (210) to move up and down so that the beam exit surface of the collimator assembly (300) actively approaches or adheres to the surface of the target area of ​​the small animal to be irradiated. as well as The verification control module is configured to perform Monte Carlo dose simulation based on the individualized image data of the irradiated small animal and the physical model of the collimator assembly (300) to generate a predicted dose distribution; and to verify the accuracy of dose delivery by comparing the measured dose distribution obtained using the collimator assembly (300) with the predicted dose distribution.

2. The small animal proton mini-beam irradiation system based on a 3D-printed collimator according to claim 1, characterized in that, The collimator assembly (300) is a structural component integrally formed by additive manufacturing technology, and has multiple parallel and penetrating micro-beam channels inside.

3. The small animal proton mini-beam irradiation system based on a 3D-printed collimator according to claim 2, characterized in that, The additive manufacturing technology is photopolymerization molding technology, and the material of the collimator assembly (300) is a photopolymerized resin composite material.

4. The small animal proton mini-beam irradiation system based on a 3D-printed collimator according to claim 2, characterized in that, The cross-sectional width of the microbeam channel is 0.4 mm to 1.0 mm, and the center distance between adjacent channels is 1.0 mm to 3.0 mm.

5. The small animal proton mini-beam irradiation system based on a 3D-printed collimator according to claim 1, characterized in that, The collimator assembly (300) includes a horizontal portion and a vertical portion: The horizontal part is embedded in the bearing platform (210), and a limiting through hole that matches the beam exit surface is provided at the center of the horizontal part; The interior of the vertical section is provided with a micro-pore array that spatially divides the incident proton beam, and one end of the vertical section is embedded in the limiting through hole and directly faces the small animal to be irradiated on the support base (110).

6. The small animal proton mini-beam irradiation system based on a 3D-printed collimator according to claim 1 or 5, characterized in that, The collimator assembly (300) has an inverted T-shaped structure.

7. The small animal proton mini-beam irradiation system based on a 3D-printed collimator according to claim 1, characterized in that, The collimator assembly (300) has a visual alignment mark on its top or outer side, which is used to align the beam channel with the target area in conjunction with an external laser positioning system.

8. The small animal proton mini-beam irradiation system based on a 3D-printed collimator according to claim 1, characterized in that, The lifting drive assembly includes a Z-axis lifting screw (221), an adjusting handwheel (222) that cooperates with the Z-axis lifting screw (221), and a guide rod (223) for guiding the direction of movement.

9. The small animal proton mini-beam irradiation system based on a 3D-printed collimator according to claim 1, characterized in that, The verification control module includes: The image processing unit is used to import and process CT images of the object to be irradiated; A Monte Carlo dose engine is used to load the digital model and material parameters of the collimator assembly and calculate the predicted dose distribution. The film dose analysis unit is used to analyze the dose image obtained after irradiation of radiochromic film, obtain the measured dose distribution, and perform Gamma pass rate analysis on the measured dose distribution and the predicted dose distribution.

10. A method for irradiating small animals with proton mini-beams based on a 3D-printed collimator according to any one of claims 1-9, characterized in that, Includes the following steps: Providing a collimator: Providing a collimator assembly with predetermined microbeam channel parameters; Dose prediction steps: Acquire target area images of the small animal to be irradiated, and perform Monte Carlo simulation based on the images and collimator components to obtain the predicted dose distribution within the target area; Dosage verification steps: Pre-irradiate the dose measurement device using a collimator assembly to obtain the measured dose distribution, and determine whether the consistency between the measured dose distribution and the predicted dose distribution meets a preset standard; Positioning and irradiation steps: If the preset standard is met, fix the small animal to the support base, adjust the position of the carrier platform to align the target area with the collimator assembly, and move the carrier platform so that the beam exit surface is in contact with the surface of the small animal target area or reaches a preset small distance, and then perform proton beam irradiation.

11. The method for irradiating small animals with proton mini-beams based on a 3D-printed collimator according to claim 10, characterized in that, If the consistency does not meet the preset standard in the dose verification step, the material parameters in the Monte Carlo simulation are adjusted or the collimator assembly is re-fabricated, and the dose prediction step and the dose verification step are re-executed.

12. The method for irradiating small animals with proton mini-beams based on a 3D-printed collimator according to claim 10, characterized in that, In the positioning irradiation step, the drive platform is raised and lowered so that the beam exit surface of the collimator assembly moves towards the small animal. The beam exit surface flattens the natural bulges on the target area surface to form a flat interface suitable for microbeam array incident.

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