基于快循环同步加速器的闪疗束流配送系统

史莹; 张满洲; 李德明; 韩学健; 孙培涵

doi:10.11884/HPLPB202537.250003

基于快循环同步加速器的闪疗束流配送系统

doi: 10.11884/HPLPB202537.250003

史莹^{1, 2,},
张满洲^{1, 2, 3, ,},
李德明^{1, 2},
韩学健^{1, 2},
孙培涵^{1, 2}

1.
中国科学院上海应用物理研究所，上海 201800
2.
中国科学院大学，北京 101408
3.
上海艾普强粒子设备有限公司，上海 201800

基金项目: 上海市质子治疗转化研究重点实验室项目

详细信息

作者简介:
史　莹，shiying@sinap.ac.cn

通讯作者:
张满洲，zhangmanzhou@sinap.ac.cn。

中图分类号: R144.1
计量
- 文章访问数: 25
- HTML全文浏览量: 13
- PDF下载量: 3
- 被引次数: 0
出版历程
- 收稿日期: 2025-01-06
- 修回日期: 2025-04-08
- 录用日期: 2025-04-07
- 网络出版日期: 2025-06-17

Design and validation of a proton beam line based on a rapid-cycling synchrotron for Flash radiation

Shi Ying^{1, 2
,},
Zhang Manzhou^{1, 2, 3
, ,},
Li Deming^{1, 2},
Han Xuejian^{1, 2},
Sun Peihan^{1, 2}

1.
Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China
2.
University of Chinese Academy of Sciences, Beijing 101408, China
3.
Shanghai Apactron Particle Equipment Co., Ltd, Shanghai 201800, China

摘要

摘要: 为了实现超高剂量率的质子Flash照射，基于快循环同步加速器建立了一个束流配送系统。快循环同步加速器能够在数百ns内快速引出质子束，通过改变不同的引出时间引出不同能量的束流，从而实现能量的快速切换。基于这个特性，考虑与层叠加照射方式相结合，束流的瞬时剂量率可以达到10⁷ Gy/s。靶区在纵向上分成单独的层，每一层需要不同的能量。由于能量层切换的时间非常短，射程调制轮无法满足需求，选用纹波过滤器进行射程调制。使用蒙特卡罗软件FLUKA模拟了整个装置，包括了散射片，射程补偿器，纹波过滤器和准直器，最大化提高进入靶区的质子通量。在低、中、高三个能量区域，根据原始布拉格峰曲线设计了三种尺寸的纹波过滤器，将尖峰区域扩展成高斯分布，分别提供了2、6、13 cm宽度的三个扩展布拉格峰区域，有效减少了能量层数量，缩短了整体照射时间。将快循环同步加速器与层叠加的照射方式相结合，可以获得超高瞬时剂量率的照射野，为实现Flash照射提供了一种新的方法。
- 质子治疗 /
- Flash效应 /
- 束流配送系统 /
- 层叠加 /
- 快循环同步加速器
Abstract: We design a proton beamline based on a rapid-cycling synchrotron for Flash radiation with ultra-high dose rate. Because proton beams can be extracted within hundreds of nanoseconds in the rapid-cycling synchrotron, its energy may be altered from one cycle to the next with different extraction time. The intended beamline system can realize layer stacking irradiation at an instantaneous dose rate of 10⁷ Gy/s. Each of longitudinal layer requires a different beam intensity. The target is divided longitudinally into different layers, each of which needs a different beam energy, in order to produce a uniform irradiation field. The system, including a double scatter system, a range compensator, a ripple filter, and a multi-leaf collimator to maximize proton fluence into the target, is simulated using the Monte Carlo software FLUKA. Three different kinds of ripple filters are built in the low, medium, and high energy zones based on the original Bragg peaks in order to decrease the number of energy layers and shorten the total irradiation duration. These filters transform the spike region into a Gaussian distribution with flat expansion areas of 2 cm, 6 cm, and 20 cm, respectively. Combining the rapid-cycling synchrotron with the layer stacking irradiation provides a novel method for realizing Flash proton irradiation, which delivers an ultra-high dose rate to the target.
- proton therapy /
- Flash effect /
- beam delivery system /
- layer stacking /
- rapid-cycling synchrotron

HTML全文

图 1 束流配送系统装置的布局示意图。装置的具体参数和之间的距离将在文章后面具体介绍

Figure 1. Location layout of the beamline modulation. A detailed description of the parameters and distances between each device will be provided later

下载: 全尺寸图片幻灯片

图 2 低能区域的柱坐标系下归一化横向剂量分布图以及直角坐标系下的质子通量

Figure 2. Transverse normalized dose profile in cylindrical coordinate system and proton fluence in rectangular coordinate system in low energy region

下载: 全尺寸图片幻灯片

图 3 中能区域的柱坐标系下归一化横向剂量分布图以及直角坐标系下的质子通量

Figure 3. Transverse normalized dose profile in cylindrical coordinate system and proton fluence in rectangular coordinate system in medium energy region

下载: 全尺寸图片幻灯片

图 4 高能区域的柱坐标系下归一化横向剂量分布图以及直角坐标系下的质子通量

Figure 4. Transverse normalized dose profile in cylindrical coordinate system and proton fluence in rectangular coordinate system in high energy region

下载: 全尺寸图片幻灯片

图 5 低、中、高能区域调制形成的SOBP结构示意图。

Figure 5. A schematic view of SOBP construction in low, medium and high energy region

下载: 全尺寸图片幻灯片

表 1 三个不同能量的质子束经过有无固体水的水箱测量数据和FLUKA模拟结果对比

Table 1. Comparison of observed data using the water phantom and FLUKA simulation results about weather passing through solid water under three different energy levels

Energy/MeV	With 5 cm solid water or no		Bragg peak/cm	R_{80_1}/cm	R_{80_2}/cm	ΔR₈₀/cm
109	no	Measurement	8.70419	8.54409	8.80425	0.26016
	no	Simulation	8.70218	8.54214	8.80220	0.26007
	with	Measurement	3.64103	3.46091	3.74109	0.28018
	with	Simulation	3.65091	3.49087	3.75094	0.26007
152	no	Measurement	15.79053	15.54036	16.00067	0.46031
	no	Simulation	15.80395	15.53388	15.98400	0.45011
	with	Measurement	10.75829	10.47688	10.92915	0.45226
	with	Simulation	10.77269	10.48262	10.93273	0.45011
235	no	Measurement	33.93419	33.37339	34.27468	0.90129
	no	Simulation	33.89847	33.34834	34.25856	0.91023
	with	Measurement	28.85285	28.31231	29.19319	0.88088
	with	Simulation	28.87722	28.31708	29.21730	0.90023

下载: 导出CSV

表 2 低能区域不同能量质子束的权重

Table 2. Weights of proton beams with different energies in low energy region

Energy/MeV	Weight	Flatness/%
70	0.042	1.68
75	0.048	2.43
80	0.062	3.12
85	0.082	3.49
90	0.114	3.65
95	0.182	3.72
100	0.470	4.90

下载: 导出CSV

表 3 中能区域不同能量质子束的权重

Table 3. Weights of proton beams with different energies in medium energy region

Energy/MeV	Weight	Flatness/%
130	0.064	5.88
135	0.024	3.57
140	0.036	3.82
145	0.071	2.25
150	0.072	1.12
155	0.104	3.91
160	0.151	4.25
165	0.478	4.88

下载: 导出CSV

表 4 高能区域不同能量质子束的权重

Table 4. Weights of proton beams with different energies in high energy region

Energy/MeV	Weight	Flatness/%
170	0.037	5.69
180	0.030	5.41
190	0.047	4.52
195	0.023	3.48
200	0.025	3.10
205	0.058	2.70
210	0.056	2.85
215	0.052	3.41
220	0.121	4.31
225	0.125	4.82
230	0.426	5.38

下载: 导出CSV

参考文献(32)

[1]	Favaudon V, Caplier L, Monceau V, et al. Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice[J]. Science Translational Medicine, 2014, 6: 245ra93.
[2]	Allen B D, Alaghband Y, Kramár E A, et al. Elucidating the neurological mechanism of the Flash effect in juvenile mice exposed to hypofractionated radiotherapy[J]. Neuro-Oncology, 2023, 25(5): 927-939. doi: 10.1093/neuonc/noac248
[3]	Ashraf M R, Melemenidis S, Liu K, et al. Multi-Institutional audit of FLASH and conventional dosimetry with a 3D printed anatomically realistic mouse phantom[J]. International Journal of Radiation Oncology · Biology · Physics, 2024, 120(1): 287-300.
[4]	Zhang Qixian, Gerweck L E, Cascio E, et al. Proton FLASH effects on mouse skin at different oxygen tensions[J]. Physics in Medicine & Biology, 2023, 68: 055010.
[5]	Montay-Gruel P, Petersson K, Jaccard M, et al. Irradiation in a flash: unique sparing of memory in mice after whole brain irradiation with dose rates above 100Gy/s[J]. Radiotherapy and Oncology, 2017, 124(3): 365-369. doi: 10.1016/j.radonc.2017.05.003
[6]	Montay-Gruel P, Acharya M M, Petersson K, et al. Long-term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species[J]. Proceedings of the National Academy of Sciences of the United States of America, 2019, 116(22): 10943-10951.
[7]	Röch T F, SZABÓZ, Haffa D, et al. A feasibility study of zebrafish embryo irradiation with laser-accelerated protons[J]. Review of Scientific Instruments, 2020, 91: 063303. doi: 10.1063/5.0008512
[8]	Beyreuther E, Brand M, Hans S, et al. Feasibility of proton FLASH effect tested by zebrafish embryo irradiation[J]. Radiotherapy and Oncology, 2019, 139: 46-50. doi: 10.1016/j.radonc.2019.06.024
[9]	Vozenin M C, De Fornel P, Petersson K, et al. The advantage of FLASH radiotherapy confirmed in mini-pig and cat-cancer patients[J]. Clinical Cancer Research, 2019, 25(1): 35-42. doi: 10.1158/1078-0432.CCR-17-3375
[10]	Bourhis J, Sozzi W J, Jorge P G, et al. Treatment of a first patient with FLASH-radiotherapy[J]. Radiotherapy and Oncology, 2019, 139: 18-22. doi: 10.1016/j.radonc.2019.06.019
[11]	Mascia A E, Daugherty E C, Zhang Yongbin, et al. Proton FLASH radiotherapy for the treatment of symptomatic bone metastases: the FAST-01 nonrandomized trial[J]. JAMA Oncology, 2023, 9(1): 62-69. doi: 10.1001/jamaoncol.2022.5843
[12]	Daugherty E C, Zhang Y, Xiao Z, et al. FLASH radiotherapy for the treatment of symptomatic bone metastases in the thorax (FAST-02): protocol for a prospective study of a novel radiotherapy approach[J]. Radiation Oncology, 2024, 19: 34. doi: 10.1186/s13014-024-02419-4
[13]	Hughes J R, Parsons J L. FLASH radiotherapy: current knowledge and future insights using proton-beam therapy[J]. International Journal of Molecular Sciences, 2020, 21: 6492. doi: 10.3390/ijms21186492
[14]	Borghini A, Labate L, Piccinini S, et al. FLASH radiotherapy: expectations, challenges, and current knowledge[J]. International Journal of Molecular Sciences, 2024, 25: 2546. doi: 10.3390/ijms25052546
[15]	Vozenin M C, Bourhis J, Durante M. Towards clinical translation of FLASH radiotherapy[J]. Nature Reviews Clinical Oncology, 2022, 19(12): 791-803. doi: 10.1038/s41571-022-00697-z
[16]	Jolly S, Owen H, Schippers M, et al. Technical challenges for FLASH proton therapy[J]. Physica Medica, 2020, 78: 71-82. doi: 10.1016/j.ejmp.2020.08.005
[17]	Manti L, Perozziello F M, Borghesi M, et al. The radiobiology of laser-driven particle beams: focus on sub-lethal responses of normal human cells[J]. Journal of Instrumentation, 2017, 12: C03084. doi: 10.1088/1748-0221/12/03/C03084
[18]	Bayart E, Flacco A, Delmas O, et al. Fast dose fractionation using ultra-short laser accelerated proton pulses can increase cancer cell mortality, which relies on functional PARP1 protein[J]. Scientific Reports, 2019, 9: 10132. doi: 10.1038/s41598-019-46512-1
[19]	Bin Jianhui, Obst-Huebl L, Mao Jianhua, et al. A new platform for ultra-high dose rate radiobiological research using the BELLA PW laser proton beamline[J]. Scientific Reports, 2022, 12: 1484. doi: 10.1038/s41598-022-05181-3
[20]	Shi Ying, Zhang Manzhou, Ouyang Lianhua, et al. Design of a rapid-cycling synchrotron for Flash proton therapy[J]. Nuclear Science and Techniques, 2023, 34: 145. doi: 10.1007/s41365-023-01283-3
[21]	Mori S, Kanematsu N, Asakura H, et al. Four-Dimensional lung treatment planning in layer-stacking carbon ion beam treatment: comparison of layer-stacking and conventional ungated/gated irradiations[J]. International Journal of Radiation Oncology · Biology · Physics, 2011, 80(2): 597-607.
[22]	Kubo N, Kubota Y, Oike T, et al. Skin dose reduction by layer-stacking irradiation in carbon ion radiotherapy for parotid tumors[J]. Frontiers in Oncology, 2020, 10: 1396. doi: 10.3389/fonc.2020.01396
[23]	Grusell E, Montelius A, Brahme A, et al. A general solution to charged particle beam flattening using an optimized dual-scattering-foil technique, with application to proton therapy beams[J]. Physics in Medicine & Biology, 1994, 39(12): 2201-2216.
[24]	Wroe A J, Schulte R W, Barnes S, et al. Proton beam scattering system optimization for clinical and research applications[J]. Medical Physics, 2013, 40: 041702. doi: 10.1118/1.4793262
[25]	Gottschalk B. On the scattering power of radiotherapy protons[J]. Medical Physics, 2010, 37(1): 352-367. doi: 10.1118/1.3264177
[26]	Kainz K K, Antolak J A, Almond P R, et al. Dual scattering foil design for poly-energetic electron beams[J]. Physics in Medicine & Biology, 2005, 50(5): 755-767.
[27]	Weber U, Kraft G. Design and construction of a ripple filter for a smoothed depth dose distribution in conformal particle therapy[J]. Physics in Medicine & Biology, 1999, 44(11): 2765-2775.
[28]	Akagi T, Higashi A, Tsugami H, et al. Ridge filter design for proton therapy at Hyogo Ion Beam Medical Center[J]. Physics in Medicine & Biology, 2003, 48(22): N301-N312.
[29]	Kang M, Pang D. Commissioning and beam characterization of the first gantry-mounted accelerator pencil beam scanning proton system[J]. Medical Physics, 2020, 47(8): 3496-3510. doi: 10.1002/mp.13972
[30]	Smith B R, Hyer D E, Hill P M, et al. Secondary neutron dose from a dynamic collimation system during intracranial pencil beam scanning proton therapy: a Monte Carlo investigation[J]. International Journal of Radiation Oncology · Biology · Physics, 2019, 103(1): 241-250.
[31]	Grewal H S, Ahmad S, Jin H. Performance evaluation of adaptive aperture’s static and dynamic collimation in a compact pencil beam scanning proton therapy system: a dosimetric comparison study for multiple disease sites[J]. Medical Dosimetry, 2021, 46(2): 179-187. doi: 10.1016/j.meddos.2020.11.001
[32]	Grewal H S, Ahmad S, Jin H. Characterization of penumbra sharpening and scattering by adaptive aperture for a compact pencil beam scanning proton therapy system[J]. Medical Physics, 2021, 48(4): 1508-1519. doi: 10.1002/mp.14771