Abstract：
BACKGROUND: The recent rediscovery of the FLASH effect, a normal tissue sparing phenomenon observed in ultra-high dose rate (UHDR) irradiations, has instigated a surge of research endeavors aiming to close the gap between experimental observation and clinical treatment. However, the dependences of the FLASH effect and its underpinning mechanisms on beam parameters are not well known, and large-scale in vivo studies using murine models of human cancer are needed for these investigations.
OBJECTIVE: To commission a high-throughput, variable dose rate platform providing uniform electron fields (≥15 cm diameter) at conventional (CONV) and UHDRs for in vivo investigations of the FLASH effect and its dependences on pulsed electron beam parameters.
METHODS: A murine whole-thoracic lung irradiation (WTLI) platform was constructed using a 1.3 cm thick Cerrobend collimator forming a 15 × 1.6 cm2 slit. Control of dose and dose rate were realized by adjusting the number of monitor units and couch vertical position, respectively. Achievable doses and dose rates were investigated using Gafchromic EBT-XD film at 1 cm depth in solid water and lung-density phantoms. Percent depth dose (PDD) and dose profiles at CONV and various UHDRs were also measured at depths from 0 to 2 cm. A radiation survey was performed to assess radioactivation of the Cerrobend collimator by the UHDR electron beam in comparison to a precision-machined copper alternative.
RESULTS: This platform allows for the simultaneous thoracic irradiation of at least three mice. A linear relationship between dose and number of monitor units at a given UHDR was established to guide the selection of dose, and an inverse-square relationship between dose rate and source distance was established to guide the selection of dose rate between 20 and 120 Gy·s-1 . At depths of 0.5 to 1.5 cm, the depth range relevant to murine lung irradiation, measured PDDs varied within ±1.5%. Similar lateral dose profiles were observed at CONV and UHDRs with the dose penumbrae widening from 0.3 mm at 0 cm depth to 5.1 mm at 2.0 cm. The presence of lung-density plastic slabs had minimal effect on dose distributions as compared to measurements made with only solid water slabs. Instantaneous dose rate measurements of the activated copper collimator were up to two orders of magnitude higher than that of the Cerrobend collimator.
CONCLUSIONS: A high-throughput, variable dose rate platform has been developed and commissioned for murine WTLI electron FLASH radiotherapy. The wide field of our UHDR-enabled linac allows for the simultaneous WTLI of at least three mice, and for the average dose rate to be modified by changing the source distance, without affecting dose distribution. The platform exhibits uniform, and comparable dose distributions at CONV and UHDRs up to 120 Gy·s-1 , owing to matched and flattened 16 MeV CONV and UHDR electron beams. Considering radioactivation and exposure to staff, Cerrobend collimators are recommended above copper alternatives for electron FLASH research. This platform enables high-throughput animal irradiation, which is preferred for experiments using a large number of animals, which are required to effectively determine UHDR treatment efficacies.
OBJECTIVE: To commission a high-throughput, variable dose rate platform providing uniform electron fields (≥15 cm diameter) at conventional (CONV) and UHDRs for in vivo investigations of the FLASH effect and its dependences on pulsed electron beam parameters.
METHODS: A murine whole-thoracic lung irradiation (WTLI) platform was constructed using a 1.3 cm thick Cerrobend collimator forming a 15 × 1.6 cm2 slit. Control of dose and dose rate were realized by adjusting the number of monitor units and couch vertical position, respectively. Achievable doses and dose rates were investigated using Gafchromic EBT-XD film at 1 cm depth in solid water and lung-density phantoms. Percent depth dose (PDD) and dose profiles at CONV and various UHDRs were also measured at depths from 0 to 2 cm. A radiation survey was performed to assess radioactivation of the Cerrobend collimator by the UHDR electron beam in comparison to a precision-machined copper alternative.
RESULTS: This platform allows for the simultaneous thoracic irradiation of at least three mice. A linear relationship between dose and number of monitor units at a given UHDR was established to guide the selection of dose, and an inverse-square relationship between dose rate and source distance was established to guide the selection of dose rate between 20 and 120 Gy·s-1 . At depths of 0.5 to 1.5 cm, the depth range relevant to murine lung irradiation, measured PDDs varied within ±1.5%. Similar lateral dose profiles were observed at CONV and UHDRs with the dose penumbrae widening from 0.3 mm at 0 cm depth to 5.1 mm at 2.0 cm. The presence of lung-density plastic slabs had minimal effect on dose distributions as compared to measurements made with only solid water slabs. Instantaneous dose rate measurements of the activated copper collimator were up to two orders of magnitude higher than that of the Cerrobend collimator.
CONCLUSIONS: A high-throughput, variable dose rate platform has been developed and commissioned for murine WTLI electron FLASH radiotherapy. The wide field of our UHDR-enabled linac allows for the simultaneous WTLI of at least three mice, and for the average dose rate to be modified by changing the source distance, without affecting dose distribution. The platform exhibits uniform, and comparable dose distributions at CONV and UHDRs up to 120 Gy·s-1 , owing to matched and flattened 16 MeV CONV and UHDR electron beams. Considering radioactivation and exposure to staff, Cerrobend collimators are recommended above copper alternatives for electron FLASH research. This platform enables high-throughput animal irradiation, which is preferred for experiments using a large number of animals, which are required to effectively determine UHDR treatment efficacies.
摘要：
背景：最近对FLASH效应的重新发现，在超高剂量率（UHDR）照射中观察到的正常组织备用现象，引发了旨在缩小实验观察与临床治疗之间差距的研究工作的激增。然而,FLASH效应及其基础机制对光束参数的依赖性尚不清楚，这些研究需要使用人类癌症的小鼠模型进行大规模的体内研究。
目标：为了实现高通量，可变剂量率平台在常规（CONV）和UHDR下提供均匀的电子场（直径≥15cm），用于体内研究FLASH效应及其对脉冲电子束参数的依赖性。
方法：使用1.3cm厚的Cerrobend准直仪形成15×1.6cm2的狭缝，构建了鼠全胸肺照射（WTLI）平台。通过调整监测单元的数量和躺椅的垂直位置来实现剂量和剂量率的控制，分别。使用GafchrorEBT-XD胶片在固体水和肺密度模型中的1cm深度研究了可实现的剂量和剂量率。还在0至2cm的深度处测量了在CONV和各种UHDR处的百分比深度剂量(PDD)和剂量曲线。与精密加工的铜替代品相比，进行了辐射调查以评估UHDR电子束对Cerrobend准直器的放射性激活。
结果：该平台允许对至少三只小鼠同时进行胸部照射。建立了剂量与给定UHDR监测单位数量之间的线性关系，以指导剂量的选择，建立剂量率与源距的平方反比关系,指导20～120Gy·s-1剂量率的选择。在0.5至1.5厘米的深度，与鼠肺照射相关的深度范围，测得的PDD在±1.5%内变化。在CONV和UHDRs观察到类似的侧向剂量曲线，剂量边缘从0厘米深度的0.3毫米扩大到2.0厘米的5.1毫米。与仅使用固体水板进行的测量相比，肺密度塑料板的存在对剂量分布的影响最小。激活的铜准直器的瞬时剂量率测量比Cerrobend准直器的瞬时剂量率测量高两个数量级。
结论：高通量，可变剂量率平台已开发并委托用于小鼠WTLI电子FLASH放射治疗。我们支持UHDR的直线加速器的广域允许至少三只小鼠同时进行WTLI，并且通过改变源距离来修改平均剂量率，不影响剂量分布。平台展示制服，在CONV和UHDRs高达120Gy·s-1的情况下，剂量分布相当，由于匹配和平坦的16MeVCONV和UHDR电子束。考虑到辐射激活和接触工作人员，Cerrobend准直器被推荐用于电子FLASH研究的铜替代品。该平台可实现高通量动物辐照，这是使用大量动物进行实验的首选，这是有效确定UHDR治疗效果所必需的。
目标：为了实现高通量，可变剂量率平台在常规（CONV）和UHDR下提供均匀的电子场（直径≥15cm），用于体内研究FLASH效应及其对脉冲电子束参数的依赖性。
方法：使用1.3cm厚的Cerrobend准直仪形成15×1.6cm2的狭缝，构建了鼠全胸肺照射（WTLI）平台。通过调整监测单元的数量和躺椅的垂直位置来实现剂量和剂量率的控制，分别。使用GafchrorEBT-XD胶片在固体水和肺密度模型中的1cm深度研究了可实现的剂量和剂量率。还在0至2cm的深度处测量了在CONV和各种UHDR处的百分比深度剂量(PDD)和剂量曲线。与精密加工的铜替代品相比，进行了辐射调查以评估UHDR电子束对Cerrobend准直器的放射性激活。
结果：该平台允许对至少三只小鼠同时进行胸部照射。建立了剂量与给定UHDR监测单位数量之间的线性关系，以指导剂量的选择，建立剂量率与源距的平方反比关系,指导20～120Gy·s-1剂量率的选择。在0.5至1.5厘米的深度，与鼠肺照射相关的深度范围，测得的PDD在±1.5%内变化。在CONV和UHDRs观察到类似的侧向剂量曲线，剂量边缘从0厘米深度的0.3毫米扩大到2.0厘米的5.1毫米。与仅使用固体水板进行的测量相比，肺密度塑料板的存在对剂量分布的影响最小。激活的铜准直器的瞬时剂量率测量比Cerrobend准直器的瞬时剂量率测量高两个数量级。
结论：高通量，可变剂量率平台已开发并委托用于小鼠WTLI电子FLASH放射治疗。我们支持UHDR的直线加速器的广域允许至少三只小鼠同时进行WTLI，并且通过改变源距离来修改平均剂量率，不影响剂量分布。平台展示制服，在CONV和UHDRs高达120Gy·s-1的情况下，剂量分布相当，由于匹配和平坦的16MeVCONV和UHDR电子束。考虑到辐射激活和接触工作人员，Cerrobend准直器被推荐用于电子FLASH研究的铜替代品。该平台可实现高通量动物辐照，这是使用大量动物进行实验的首选，这是有效确定UHDR治疗效果所必需的。
