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建立使用激光加速电子进行细胞辐照实验的技术前提。

Establishment of technical prerequisites for cell irradiation experiments with laser-accelerated electrons.

机构信息

Forschungszentrum Dresden-Rossendorf P.O. Box 510119, Bautzner Landstrafe 400, D-01314 Dresden, Germany.

出版信息

Med Phys. 2010 Apr;37(4):1392-400. doi: 10.1118/1.3301598.

Abstract

PURPOSE

In recent years, laser-based acceleration of charged particles has rapidly progressed and medical applications, e.g., in radiotherapy, might become feasible in the coming decade. Requirements are monoenergetic particle beams with long-term stable and reproducible properties as well as sufficient particle intensities and a controlled delivery of prescribed doses at the treatment site. Although conventional and laser-based particle accelerators will administer the same dose to the patient, their different time structures could result in different radiobiological properties. Therefore, the biological response to the ultrashort pulse durations and the resulting high peak dose rates of these particle beams have to be investigated. The technical prerequisites, i.e., a suitable cell irradiation setup and the precise dosimetric characterization of a laser-based particle accelerator, have to be realized in order to prepare systematic cell irradiation experiments.

METHODS

The Jena titanium:sapphire laser system (JETI) was customized in preparation for cell irradiation experiments with laser-accelerated electrons. The delivered electron beam was optimized with regard to its spectrum, diameter, dose rate, and dose homogeneity. A custom-designed beam and dose monitoring system, consisting of a Roos ionization chamber, a Faraday cup, and EBT-1 dosimetry films, enables real-time monitoring of irradiation experiments and precise determination of the dose delivered to the cells. Finally, as proof-of-principle experiment cell samples were irradiated using this setup.

RESULTS

Laser-accelerated electron beams, appropriate for in vitro radiobiological experiments, were generated with a laser shot frequency of 2.5 Hz and a pulse length of 80 fs. After laser acceleration in the helium gas jet, the electrons were filtered by a magnet, released from the vacuum target chamber, and propagated in air for a distance of 220 mm. Within this distance a lead collimator (aperture of 35 mm) was introduced, leading, along with the optimized setup, to a beam diameter of 35 mm, sufficient for the irradiation of common cell culture vessels. The corresponding maximum dose inhomogeneity over the beam spot was less than 10% for all irradiated samples. At cell position, the electrons posses a mean kinetic energy of 13.6 MeV, a bunch length of about 5 ps (FWHM), and a mean pulse dose of 1.6 mGy/bunch. Cross correlations show clear linear dependencies for the online recorded accumulated bunch charges, pulse doses, and pulse numbers on absolute doses determined with EBT-1 films. Hence, the established monitoring system is suitable for beam control and a dedicated dose delivery. Additionally, reasonable day-to-day stable and reproducible properties of the electron beam were achieved.

CONCLUSIONS

Basic technical prerequisites for future cell irradiation experiments with ultrashort pulsed laser-accelerated electrons were established at the JETI laser system. The implemented online control system is suitable to compensate beam intensity fluctuations and the achieved accuracy of dose delivery to the cells is sufficient for radiobiological cell experiments. Hence, systematic in vitro cell irradiation experiments can be performed, being the first step toward clinical application of laser-accelerated particles. Further steps, including the transfer of the established methods to experiments on higher biological systems or to other laser-based particle accelerators, will be prepared.

摘要

目的

近年来,基于激光的带电粒子加速技术发展迅速,在未来十年内,医学应用,如放射治疗,可能成为可行的选择。该技术需要具备以下特性:单能粒子束,具有长期稳定且可重复的特性,以及足够的粒子强度和可控制地将规定剂量递送至治疗部位。尽管传统和基于激光的粒子加速器将向患者提供相同的剂量,但它们不同的时间结构可能导致不同的放射生物学特性。因此,必须研究这些粒子束的超短脉冲持续时间和由此产生的高峰剂量率对细胞的生物学响应。为了准备系统的细胞辐照实验,必须实现技术前提,即合适的细胞辐照装置和基于激光的粒子加速器的精确剂量学特性。

方法

为了准备使用激光加速电子进行细胞辐照实验,对耶拿钛宝石激光系统(JETI)进行了定制。根据其光谱、直径、剂量率和剂量均匀性对输送的电子束进行了优化。一个定制的光束和剂量监测系统,由 Roos 电离室、法拉第杯和 EBT-1 剂量测定胶片组成,可实时监测辐照实验并精确确定递送至细胞的剂量。最后,使用该装置对细胞样本进行了初步的实验性辐照。

结果

使用激光shot 频率为 2.5 Hz 和脉冲长度为 80 fs 的激光加速技术,生成了适用于体外放射生物学实验的电子束。氦气射流中的电子经过激光加速后,通过磁铁过滤、从真空靶室释放,并在空气中传播 220mm 的距离。在这段距离内,引入了一个铅准直器(孔径为 35mm),与优化后的装置一起,使光束直径达到 35mm,足以辐照常见的细胞培养容器。所有辐照样品的光束光斑内的最大剂量不均匀性均小于 10%。在细胞位置,电子具有平均动能 13.6MeV、束长约 5ps(半高全宽)和平均脉冲剂量 1.6mGy/脉冲。在线记录的累积脉冲电荷量、脉冲剂量和脉冲数与 EBT-1 胶片确定的绝对剂量之间存在明显的线性相关性。因此,建立的监测系统适用于束流控制和专用剂量传递。此外,还实现了电子束具有合理的日间稳定和可重复性的基本技术前提。

结论

在 JETI 激光系统上建立了用于未来使用超短脉冲激光加速电子进行细胞辐照实验的基本技术前提。所实现的在线控制系统适用于补偿束流强度波动,并且对细胞的剂量传递精度足以满足放射生物学细胞实验的要求。因此,可以进行系统的体外细胞辐照实验,这是将激光加速粒子应用于临床的第一步。下一步将准备将已建立的方法转移到更高的生物系统或其他基于激光的粒子加速器的实验中。

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