New technologies for a clinical establishment of microbeam radiation therapy

微束放射治疗(MRT)是放射肿瘤学中的一种创新的临床前方法，它利用平行、几十微米宽和几个100微米分离的束流阵列。各种临床前研究表明，在相同的肿瘤控制概率下，这些空间分割的辐射场对健康的肿瘤周围组织的毒性远低于均匀辐射场。因此，预计脑肿瘤和肺癌的放射治疗都将带来显著的好处，因为肺癌周围正常组织的敏感性限制了更高治疗剂量的应用。到目前为止，临床上相关的微束只能在大型的第三代同步加速器上产生，例如格勒诺布尔的欧洲同步加速器。为了临床翻译MRT，也为了临床前研究，迫切需要替代的策略来产生微束，这是本项目提案的目的。该项目由两部分组成。在第一部分中，将为小型动物照射器开发一种特殊的多缝准直器，以产生用于临床前体内研究的微束。未来，该装置将用于慕尼黑理工大学的放射生物学研究。在该项目的第二部分，将进一步开发由申请人设计的紧凑型微束源的概念，以便在随后的项目中建立原型。这项规划研究包括各种数值模拟和对辐射源各部件的技术解决方案的调查。该项目完成后，小型动物微束源将用于生物体外和体内研究以及MRT背后机制的研究，而不需要在大型同步加速器设施中使用昂贵而稀缺的束流时间。在构建临床前信息源时获得的经验将有助于未来临床概念的实现。除了微束放射治疗外，紧凑型临床微束源的概念也可能对相衬成像产生极大的兴趣。

MIcrobeam radiation therapy (MRT) is an innovative, but still preclinical approach in radiation oncology that exploits arrays of parallel, a few tens of µm wide and a few 100 µm separated beamlets. Various preclinical studies showed that these spatially fractionated radiation fields are far less toxic to healthy, tumour surrounding tissue than homogeneous radiation fields at equivalent tumour control probability. Therefore a significant benefit is expected for the radiation therapy treatment of brain tumours, but also lung tumours, where the sensitivity of the surrounding normal tissue limits the application of higher therapeutic doses. So far clinically relevant microbeams can only be generated at large third generation synchrotrons such as the European Synchrotron in Grenoble. For a clinical translation of MRT, but also for preclinical research, alternative strategies to produce microbeams are urgently required, which is the aim of this project proposal.The project consists of two parts. In the first part a special multislit collimator will be developed for a small animal irradiator to produce microbeams for preclinical in-vivo research. In the future the device will be used for radiobiological research at the technical university Munich. In the second part of the project a concept of a compact microbeam source, which was worked out by the applicant, will be further developed, such that a prototype may be built in a subsequent project. This planning study comprises various numerical simulations and the investigation of technical solutions for the various components of the radiation source. After this project the small animal microbeam source will be used for biological in-vitro and in-vivo research and the investigation of the mechanisms behind MRT, without the need to use expensive and scarce beam time at large synchrotron facilities. The experience gained when constructing the preclinical source will contribute to a future realisation of the clinical concept. Apart from microbeam radiation therapy, the concept of the compact clinical microbeam source may also be of great interest to phase contrast imaging.