A beam delivery system suitable for FLASH therapy with a variable energy linear accelerator

Abstract

The present invention discloses a beam delivery system suitable for variable-energy linear accelerator FLASH therapy. The system adopts a combination of linear accelerator variable energy and transverse scanning to achieve longitudinal depth coverage through rapid linear accelerator energy variation. There are two transverse implementation methods, including pencil beam two-dimensional point scanning and triangular wave or sine wave one-dimensional scanning, which directly completes three-dimensional conformal irradiation without the need for customized ridge filters, avoiding manufacturing difficulties caused by the complex shape of the target area, reducing costs and improving versatility.

Description

Technical Field

[0001] The present invention belongs to the technical field of irradiation radiotherapy, and in particular relates to a beam delivery system suitable for variable energy linear accelerator FLASH treatment. Background Art

[0002] Existing conventional radiotherapy devices damage cancer cells through ionizing radiation, leading to their death. However, radiotherapy also causes acute and chronic toxicity to normal tissues surrounding the tumor. These radiation-induced toxicities limit the radiation dose delivered to the tumor, thereby restricting the localized control effect of radiotherapy on the tumor.

[0003] Flash (FLASH) radiotherapy is a radiotherapy treatment that utilizes ultra-high dose rate radiation to protect normal tissue. FLASH radiotherapy requires a dose of >40 Gy to be delivered in less than 1 second, so beam delivery is a major obstacle to its application. Currently, in treatments or research aimed at achieving the FLASH effect, the approach to meeting ultra-high dose rates is to reduce the target volume, such as to 2cm×2cm or 3cm×3cm. To achieve the FLASH effect in a target volume of 10cm×10cm×10cm, the average intensity of the scattered irradiation beam must be at least greater than 700nA.

[0004] While passive delivery can achieve two- or three-dimensional conformality, beam utilization is low. For example, for protons with an incident energy of 230 MeV (~39 cm), beam transmission efficiency is only 10% when the energy drops to 170 MeV (~17 cm), and less than 1% at 70 MeV (~4 cm). Using two-dimensional conformal irradiation results in higher doses to normal tissue and a higher dose per dose, potentially causing significant side effects in patients. Using three-dimensional conformal irradiation requires that the grating aperture shape be changed on the order of milliseconds at each energy slice, with the fastest grating change time being 0.2 seconds. Therefore, with current technology, passive delivery cannot meet the irradiation requirements of FLASH radiotherapy.

[0005] Active delivery delivers three-dimensional conformal irradiation layer by layer to the tumor. For synchrotron and linear accelerators, when the output beam intensity is 700 nA, the accelerator needs to deliver multiple beams (for example, for a 10 cm × 10 cm × 10 cm tumor, the typical value is 32) within 1 second. Each energy layer must scan and irradiate thousands of target points in approximately 30 milliseconds, meaning the dwell time at each target is 30 µs, and the magnet scanning frequency is 30 kHz. Currently, dose monitoring and scanning speeds cannot meet these requirements, and therefore do not meet the dose rate delivery requirements for three-dimensional conformal irradiation required for FLASH radiotherapy.

[0006] Previously, a Chinese invention patent application, publication number CN114452550A, proposed a beam delivery system that combines longitudinal expansion of a ridge filter with transverse scanning. Using existing scanning technology, this system could achieve dose delivery sufficient for FLASH therapy. However, the ridge filter required customization based on the depth, direction, and shape of each patient's target area, resulting in limited versatility. Furthermore, complex or irregular target areas necessitated extremely high manufacturing precision, potentially significantly increasing process complexity and costs.

[0007] Furthermore, low-frequency linear accelerators, which mostly operate at frequencies ranging from tens to hundreds of MHz, are long, have large lateral dimensions, and exhibit high flux intensities, resulting in high costs. These devices are primarily used for basic scientific research and are difficult to apply in radiotherapy. High-frequency linear accelerators, while cost-effective and compact, suffer from low flux intensities, with peak intensities reaching only a few hundred µA and average fluxes in the hundreds of nanoamperes. These intensities also fall short of the requirements for 3D conformal FLASH radiotherapy. Summary of the Invention

[0008] The present invention aims to address at least one of the technical problems existing in the prior art. To this end, the present invention provides a beam delivery system suitable for variable energy linear accelerator FLASH therapy, designed to achieve three-dimensional conformal proton beam irradiation and improve the accuracy and efficiency of cancer radiotherapy.

[0009] To achieve the above object, the present invention adopts the following technical solutions:

[0010] In a first aspect, the present invention provides a beam delivery system suitable for FLASH therapy using a variable energy linear accelerator, characterized in that it includes a plurality of quadrupole magnets, a Y-direction scanning magnet, an X-direction scanning magnet, a stripe ionization chamber, a dose ionization chamber, and a therapy control system arranged in sequence along the beam transmission direction; wherein the quadrupole magnet is used to expand the diameter of the field of view of a macro bunch of a proton beam emitted by the variable energy linear accelerator to a specified size; the Y-direction scanning magnet is used to deflect the beam in the transverse y-direction; the X-direction scanning magnet is used to deflect the beam in the transverse x-direction; the stripe ionization chamber is used to measure the position of the beam in real time; the dose ionization chamber is used to measure the irradiation dose of the beam in real time; the therapy control system includes: a calibration module for calibrating the dose of the macro bunch of the proton beam in each energy layer; a demand setting module for determining the number of particles to be irradiated at each target point in the target area according to the FLASH irradiation requirements; and an accelerator control module for controlling the variable energy linear accelerator to use a pencil beam scanning mode to perform point-by-point irradiation in the transverse direction according to the determined number of particles.

[0011] Preferably, when the average beam intensity is increased to several μA, at the same dose, the quadrupole magnet increases the field of view of each macro bunch to a diameter of more than 20 mm.

[0012] Preferably, the variable energy linear accelerator rapidly changes energy by presetting the phases and amplitudes of multiple cavities. The energy is varied in a fixed point and range manner. The energy variation time is in the ms level, the energy variation step is less than 1 MeV, the macro bunch pulse length of the proton beam is controlled by a beam chopper, the pulse length variation step is less than 2 ns, and a layered scanning method is adopted longitudinally, with the far end first and the proximal end later.

[0013] In a second aspect, the present invention provides another beam delivery system suitable for FLASH therapy using a variable energy linear accelerator, characterized in that it includes a plurality of quadrupole-octupole-dodecopole combination magnets arranged in sequence along the beam transmission direction, a scanning magnet, a stripe ionization chamber, a dose ionization chamber, and a treatment control system; wherein the quadrupole-octupole-dodecopole combination magnet is used to stretch a macrobunch of a proton beam emitted by the variable energy linear accelerator in the transverse x-direction;

[0014] The scanning magnet is used to enable the macro bunch to achieve triangular wave or sine wave one-dimensional scanning in the transverse y direction; the stripe ionization chamber is used to measure the position of the beam in real time; the dose ionization chamber is used to measure the irradiation dose of the beam in real time; the treatment control system includes: a calibration module, used to calibrate the dose of the macro bunch of the proton beam in each energy layer; a demand setting module, used to determine the number of particles to be irradiated at each target point in the target area according to the FLASH irradiation requirements; and an accelerator control module, used to control the variable energy linear accelerator to use a triangular wave or sine wave one-dimensional scanning mode to perform point-by-point irradiation in the transverse y direction according to the determined number of particles.

[0015] Preferably, when the average beam intensity is increased by about 3-3.5 μA, at the same dose, the quadrupole-octupole-dodecopole combination magnet stretches each macrobunch in the transverse x-direction to obtain a macrobunch with a length of less than 100 mm and a width of more than 4.3 mm.

[0016] Preferably, the variable energy linear accelerator rapidly changes energy by presetting the phases and amplitudes of multiple cavities. The energy is varied in a fixed point and range manner. The energy variation time is in the ms level, the energy variation step is less than 1 MeV, the macro bunch pulse length of the proton beam is controlled by a beam chopper, the pulse length variation step is less than 2 ns, and a layered scanning method is adopted longitudinally, with the far end first and the proximal end later.

[0017] The present invention has the following advantages due to the adoption of the above technical solution:

[0018] 1. The beam delivery system provided by the present invention can achieve a significant change in the lateral size and distribution of the beam, with the maximum lateral size ratio of about 25 times. Therefore, single-energy layer lateral scanning irradiation can be completed through one-dimensional scanning such as triangular wave or sine wave, thereby improving irradiation efficiency.

[0019] 2. The variable energy linear accelerator can adjust the beam energy in the millisecond level, providing a bunch with a maximum of approximately 32 energy points in seconds or 5-6 different energy points in less than 200 milliseconds. It flexibly combines transverse active scanning and spatial segmentation effects to achieve efficient three-dimensional irradiation at a scanning frequency of less than 1 kHz, meeting the dose rate requirements of three-dimensional conformal irradiation.

[0020] 3. The present invention achieves longitudinal depth coverage through rapid energy change of the linear accelerator, and combines it with transverse active scanning to directly complete three-dimensional conformal irradiation without the need for customized ridge filters. This can avoid manufacturing difficulties caused by the complex shape of the target area, reduce costs and improve versatility. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Various other advantages and benefits will become apparent to those skilled in the art upon reading the detailed description of the preferred embodiment below. The accompanying drawings are for illustration purposes only and are not to be considered as limiting the present invention. Throughout the drawings, the same reference numerals are used to denote the same components. In the drawings:

[0022] Figure 1 This is a scanning principle diagram of the pencil beam two-dimensional point scanning method;

[0023] Figure 2 A schematic structural diagram of a pencil beam two-dimensional point scanning beam delivery system provided in Example 1 of the present invention;

[0024] Figure 3 Flow chart of the pencil beam two-dimensional point scanning beam delivery method provided in Example 1 of the present invention;

[0025] Figure 4 Scanning principle diagram for one-dimensional scanning methods such as triangle wave or sine wave;

[0026] Figure 5 A schematic structural diagram of a one-dimensional scanning beam delivery system such as a triangular wave or a sine wave provided in Example 2 of the present invention;

[0027] Figure 6 This is a flow chart of a one-dimensional scanning beam delivery method using a triangular wave or a sine wave, etc., provided in Example 2 of the present invention. DETAILED DESCRIPTION

[0028] To make the objectives, technical solutions, and advantages of the present invention more apparent, specific embodiments of the present invention are further described below with reference to the accompanying drawings. Although exemplary embodiments of the present invention are shown in the accompanying drawings, it should be understood that the present invention can be implemented in various forms and should not be limited by the embodiments described herein. Rather, these embodiments are provided to enable a more thorough understanding of the present invention and to fully convey the scope of the present invention to those skilled in the art.

[0029] In the description of the present invention, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inside", "outside", "clockwise", "counterclockwise", "axial", "radial", "circumferential" and the like to indicate orientations or positional relationships based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as limiting the present invention.

[0030] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of the technical features being referred to. Thus, a feature identified as "first" or "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, "plurality" means more than two, unless otherwise specifically defined.

[0031] In the present invention, unless otherwise expressly specified or limited, the terms "mounted," "connected," "connect," "fixed," etc. should be understood broadly. For example, they may refer to fixed connection, detachable connection, or integration; mechanical connection or electrical connection; direct connection or indirect connection through an intermediate medium; internal communication between two components or interaction between two components. Those skilled in the art will understand the specific meanings of the above terms in the present invention based on specific circumstances.

[0032] In the present invention, unless otherwise expressly specified or limited, when a first feature is "above" or "below" a second feature, it may mean that the first and second features are in direct contact, or that the first and second features are in indirect contact through an intermediary. Furthermore, when a first feature is "above," "above," or "above" a second feature, it may mean that the first feature is directly above or diagonally above the second feature, or simply means that the first feature is at a higher level than the second feature. When a first feature is "below," "below," or "below" a second feature, it may mean that the first feature is directly below or diagonally below the second feature, or simply means that the first feature is at a lower level than the second feature.

[0033] In the description of this specification, the reference terms "one embodiment," "some embodiments," "example," "specific example," or "some examples" mean that the specific features, structures, materials, or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described can be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art can combine and combine different embodiments or examples described in this specification and features of different embodiments or examples without contradiction.

[0034] Hereinafter, a beam delivery system suitable for FLASH proton therapy provided by an embodiment of the present invention will be described in detail with reference to the accompanying drawings.

[0035] This invention provides a beam delivery system that combines linear accelerator energy variation with transverse scanning. The variable-energy linear accelerator achieves rapid beam energy variation in the longitudinal direction, while two transverse approaches are available: pencil beam two-dimensional point scanning or triangular wave one-dimensional scanning, thereby achieving three-dimensional dose delivery across the entire target area. Due to the scanning irradiation method, proton utilization is high, and the single-point demand is an order of magnitude lower, requiring 10e9-10e10 particles per scanning point.

[0036] Example 1

[0037] This embodiment provides a pencil beam two-dimensional point scanning beam delivery system. In this embodiment, when the average beam intensity is increased to several µA (e.g., 3-3.5 µA), the field of view of each macrobunch can be increased to a diameter of more than 20 mm at the same dose. Pencil beam two-dimensional point scanning is used with a step size of 20 mm. Each dimension is scanned five times, for a total of 25 two-dimensional scans. The number of bunches is sufficient, and the magnet scanning frequency does not exceed 1 kHz, which also meets the requirements. Figure 1 The image shows the scanning process of a pencil beam two-dimensional point scanning on a 10cm*10cm area. The red arrow indicates the motion trajectory of the beam spot.

[0038] See also Figure 2The beam distribution system provided in this embodiment includes a plurality of quadrupole magnets 1, a Y-direction scanning magnet 2, an X-direction scanning magnet 3, a stripe ionization chamber 4, a dose ionization chamber 5, and a treatment control system (not shown in the figure) arranged in sequence along the beam transmission direction. Among them, the quadrupole magnet 1 is used to expand the diameter of the field of view of the macro bunch of the proton beam emitted by the variable energy linear accelerator to a specified size; the Y-direction scanning magnet 2 is used to deflect the beam in the transverse y direction; the X-direction scanning magnet 3 is used to deflect the beam in the transverse x direction; the stripe ionization chamber is used to measure the position of the beam in real time; the dose ionization chamber is used to measure the irradiation dose of the beam in real time; the treatment control system is provided with a calibration module, a demand setting module, and an accelerator control module. The calibration module is used to calibrate the dose of the macro bunch of the proton beam of each energy layer; the demand setting module is used to determine the number of particles to be irradiated at each target point in the target area 8 according to the FLASH irradiation requirements; the accelerator control module is used to control the variable energy linear accelerator to use a pencil beam scanning mode to perform point-by-point irradiation in the transverse direction according to the determined number of particles (see Figure 1 ).

[0039] Compared to beam delivery systems using longitudinally modulated transverse scanning schemes for monoenergetic proton beams, this embodiment utilizes a variable-energy linear accelerator to achieve rapid exit beam energy variation and pulse length control, enabling the pencil beam to irradiate the entire longitudinal depth of the target region and distributing the dose as close to the target region as possible. This eliminates the need for compensators and ridge filters, significantly reducing treatment costs and simplifying the treatment process while also enabling precise dose control. The variable-energy linear accelerator rapidly varies energy by presetting the phases and amplitudes of multiple cavities. Energy variation utilizes fixed-point and range energy variation, typically with fixed energies such as 150 MeV and 230 MeV. Energy variation time is in the millisecond range, and the energy step size can be less than 1 MeV. A beam chopper controls the proton beam's macrobunch pulse length, with a pulse length variation step size of less than 2 ns. A layered scanning method, first distal and then proximal, is employed longitudinally. Multiple quadrupole magnets 1 not only maintain high beam quality but also expand the diameter of the macrobunch's field of view. As the average beam intensity increases, the field of view of each macrobunch also increases at the same dose. When the average beam intensity is about 3~3.5µA, the field of view of each macrobunch can be increased to more than 20mm in diameter.

[0040] See also Figure 3 When the beam distribution system provided in the above embodiment is used, the process of completing beam distribution is as follows:

[0041] S100. Expanding the diameter of the field of view of the macro bunch of the pencil beam by using a plurality of quadrupole magnets 1 (for example, increasing the diameter to 20 mm);

[0042] S200. Calibrate and adjust the dose of the pencil beam macro bunch at each energy layer;

[0043] S300. According to the requirements of FLASH irradiation, determine the number of particles to be irradiated at each target point on the target area 8;

[0044] S400. The variable energy linear accelerator uses pencil beam scanning mode to irradiate according to the number of particles determined in step S300. To accurately distribute the proton beam dose, it is also necessary to adjust the irradiation dose by combining the variable energy linear accelerator's control of the proton beam macrobunch pulse length, ultimately providing a proton beam with a corresponding number of particles at the corresponding target point. The proton beam is sequentially irradiated to the corresponding target point in the target area 8 through the Y-scanning magnet 2, the X-scanning magnet 3, the stripe ionization chamber 4, and the dose ionization chamber 5.

[0045] In the above embodiment, preferably, if the target area 8 is larger than the set area (for example, 10 cm*10 cm), and the dose rate required for FLASH irradiation during the irradiation process cannot meet the coverage of the entire target area 8, the target area 8 is irradiated in different regions, that is, the target area 8 is divided into several regions, and only the dose coverage of a certain area in the target area is performed in one cycle, so that the area meets the FLASH irradiation requirements, and so on, until the dose coverage of all areas in the target area 8 is completed.

[0046] Example 2

[0047] This embodiment provides a one-dimensional scanning beam delivery system using a triangular wave or a sine wave. In this embodiment, when the average beam intensity is increased to several µA (e.g., 3 to 3.5 µA), at the same dose, each macrobunch is stretched in the lateral x-direction to obtain a macrobunch with a length of less than 100 mm and a width of more than 4.3 mm. A one-dimensional scan using a triangular wave or a sine wave is performed in the lateral y-direction with a step size of 3 mm. Approximately 30 scans are required. The number of beambunches is sufficient, and the magnet scanning frequency does not exceed 1 kHz, which also meets the requirements. Figure 4 The image shows the scanning process of a one-dimensional scan such as a triangle wave or a sine wave on a 10cm*10cm area. The red arrow is the movement trajectory of the beam spot.

[0048] See also Figure 5The beam delivery system provided in this embodiment includes a plurality of quadrupole-octupole-dodecopole combination magnets 6 arranged in sequence along the beam transmission direction, a scanning magnet 7, a stripe ionization chamber 4, a dose ionization chamber 5 and a treatment control system (not shown in the figure). Among them, the quadrupole-octupole-dodecole combination magnet 6 is used to stretch the macrobunch of the proton beam emitted by the variable-energy linear accelerator in the transverse x direction to obtain a macrobunch with a size of 100 mm*4.3 mm; the scanning magnet 7 is used to enable the macrobunch to achieve one-dimensional scanning such as triangular wave or sine wave in the transverse y direction; the striped ionization chamber 3 is used to measure the position of the beam in real time; the dose ionization chamber 4 is used to measure the irradiation dose of the beam in real time; the treatment control system is provided with a calibration module, a demand setting module and an accelerator control module. The calibration module is used to calibrate the dose of the macrobunch of the proton beam of each energy layer; the demand setting module is used to determine the number of particles to be irradiated at each target point in the target area 8 according to the FLASH irradiation requirements; the accelerator control module is used to control the variable-energy linear accelerator to use a one-dimensional scanning mode such as triangular wave or sine wave to perform point-by-point irradiation in the transverse y direction according to the determined number of particles.

[0049] Compared with Example 1, this embodiment no longer uses only the quadrupole magnet 1 to expand the diameter of the field of view of the macrobunch. Instead, a quadrupole-octupole-dodecopole combination magnet 6 is used to stretch each macrobunch in the transverse x-direction to obtain a macrobunch with a length of less than 100 mm and a width of more than 4.3 mm. A one-dimensional scan such as a triangular wave or a sine wave is performed in the transverse y-direction. Therefore, compared with Solution 1, one set of scanning magnets is missing, which further reduces production costs and improves flexibility of use.

[0050] See also Figure 6 Based on the beam distribution system provided in the above embodiment, this solution also provides a beam distribution method, including the following steps:

[0051] S100. Each macro bunch is stretched in the transverse x direction by a quadrupole-octupole-dodecopole combination magnet 6 to obtain a macro bunch of size 100 mm * 4.3 mm;

[0052] S200. Calibrate and adjust the dose of the proton beam macro bunch of each energy layer;

[0053] S300. According to the requirements of FLASH irradiation, determine the number of particles to be irradiated at each target point on the target area 8;

[0054] S400. The variable energy linear accelerator uses a one-dimensional scanning mode such as a triangular wave or a sine wave to irradiate according to the number of particles determined in step S300. In order to accurately distribute the dose of the proton beam, it is also necessary to adjust the irradiation dose by combining the linear accelerator to control the macro-bunch pulse length of the proton beam, and ultimately provide a proton beam with a corresponding number of particles at the corresponding target point, and irradiate the corresponding target point in the target area 8 through the scanning magnet 3, the stripe ionization chamber 4 and the dose ionization chamber 5 in sequence.

[0055] In the above embodiment, preferably, if the target area 8 is larger than the set area (for example, 10 cm*10 cm), and the dose rate required for FLASH irradiation during the irradiation process cannot meet the coverage of the entire target area 8, the target area 8 is irradiated in different regions, that is, the target area 8 is divided into several regions, and only the dose coverage of a certain area in the target area 8 is performed in one cycle, so that the area meets the FLASH irradiation requirements, and so on, until the dose coverage of all areas in the target area 8 is completed.

[0056] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present application, rather than to limit them. Although the present application has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some or all of the technical features therein. These modifications or replacements do not deviate the essence of the corresponding technical solutions from the scope of the technical solutions of the embodiments of the present application, and they should all be included in the scope of the claims and specification of the present application. In particular, as long as there is no structural conflict, the various technical features mentioned in the various embodiments can be combined in any way. The present application is not limited to the specific embodiments disclosed herein, but includes all technical solutions that fall within the scope of the claims.

Claims

1. A beam delivery system suitable for variable energy linear accelerator FLASH therapy, characterized by: It includes a plurality of quadrupole magnets, a Y-direction scanning magnet, an X-direction scanning magnet, a stripe ionization chamber, a dose ionization chamber and a treatment control system arranged in sequence along the beam transmission direction; wherein, The quadrupole magnet is used to expand the diameter of the field of view of the macro bunch of the proton beam emitted by the variable energy linear accelerator to a specified size; The Y-direction scanning magnet is used to deflect the beam in the transverse y-direction; The X-direction scanning magnet is used to deflect the beam in the transverse x-direction; The stripe ionization chamber is used to measure the position of the beam in real time; The dose ionization chamber is used to measure the irradiation dose of the beam in real time; The treatment control system comprises: A calibration module is used to calibrate the dose of the proton beam macro bunch at each energy layer; The demand setting module is used to determine the number of particles that should be irradiated on each target point in the target area according to the FLASH irradiation requirements; an accelerator control module, configured to control the variable energy linear accelerator to perform point-by-point irradiation in a transverse direction according to a determined number of particles using a pencil beam scanning mode; The variable energy linear accelerator rapidly changes energy by pre-setting the phases and amplitudes of multiple cavities. The energy variation adopts a fixed point and range energy variation method, the energy variation time is in the millisecond level, the energy variation step is less than 1MeV, the macro bunch pulse length of the proton beam is controlled by a beam chopper, the pulse length variation step is less than 2ns, and a layered scanning method is adopted in the longitudinal direction, starting from the far end and then the near end.

2. The beam distribution system according to claim 1, characterized in that: When the average beam intensity is increased to several µA, at the same dose, the quadrupole magnet increases the field of view of each macro bunch to a diameter of more than 20 mm.

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