Commissioning, characterization and first high dose rate irradiations at a compact X-ray tube for microbeam and minibeam radiation therapy

Abstract

Minibeam and microbeam radiation therapy promise improved treatment outcomes through reduced normal tissue toxicity at better tumor control rates. The lack of suitable compact radiation sources limits the clinical application of minibeams to superficial tumors and renders it impossible for microbeams. We developed the first prototype of a compact line-focus X-ray tube (LFXT) with technology potentially suitable for clinical translation of minibeams and microbeams. We give an overview of the commissioning process preceding first operation, present optical and radiological focal spot characterization methods, and dosimetric measurements. Additionally, we report on first preclinical in vitro cell and in vivo mouse brain irradiations conducted with the LFXT prototype. The LFXT was high voltage conditioned up to 300 kV.The focal spot characterization resulted in a strongly eccentric electron distribution with a width of 72.3 $\mu$m. Dosimetry showed sharp microbeam dose profiles with steep lateral penumbras and a peak-to-valley dose ratio above 10 throughout a 70 mm thick PMMA phantom. An open-field dose rate of 4.3 Gy/s was measured at an acceleration voltage of 150 kV and a beam current of 17.4 mA at 150 mm distance from the focal spot. In vitro and in vivo experiments demonstrated the feasibility of the LFXT for minibeam and microbeam applications with field sizes of 1.5-2 cm. The mice displayed no observable side effects after whole-brain 260 $\mu$m-minibeam irradiation. We successfully constructed and commissioned the first proof-of-concept LFXT prototype. Dosimetric characterizations of the achieved microbeam field showed the superiority of the LFXT compared to conventional X-ray tubes in terms of beam quality. In future developments, the remaining limitations of the prototype will be addressed for improved minibeam and first ever microbeam radiation therapy in a clinical setting.