Abstract
Microbeam Radiation Therapy is an innovative pre-clinical strategy which uses arrays of parallel, tens of micrometres wide kilo-voltage photon beams to treat tumours. These x-ray beams are typically generated on a synchrotron source. It was shown that these beam geometries allow exceptional normal tissue sparing from radiation damage while still being effective in tumour ablation. A final biological explanation for this enhanced therapeutic ratio has still not been found, some experimental data support an important role of the vasculature. In this work, the effect of microbeams on a normal microvascular network of the cerebral cortex was assessed in computer simulations and compared to the effect of homogeneous, seamless exposures at equal energy absorption. The anatomy of a cerebral microvascular network and the inflicted radiation damage were simulated to closely mimic experimental data using a novel probabilistic model of radiation damage to blood vessels. It was found that the spatial dose fractionation by microbeam arrays significantly decreased the vascular damage. The higher the peak-to-valley dose ratio, the more pronounced the sparing effect. Simulations of the radiation damage as a function of morphological parameters of the vascular network demonstrated that the distribution of blood vessel radii is a key parameter determining both the overall radiation damage of the vasculature and the dose-dependent differential effect of microbeam irradiation.
Highlights
Microbeam radiation therapy (MRT) is an emerging pre-clinical treatment strategy for cancer and considered as a promising alternative to ablate brain tumours in children (Laissue et al 2007, Slatkin et al 2009)
We compared the effects of broad-beam irradiation (BB) and microbeam irradiation (MBI) on a normal vascular network using computer simulations to better understand the sparing effect of MRT on normal tissue
We examined the influence of beam spacing, beam direction, the ratio of peak to valley dose (PVDR) and vascular network morphology on the damage inflicted on the vasculature
Summary
Microbeam radiation therapy (MRT) is an emerging pre-clinical treatment strategy for cancer and considered as a promising alternative to ablate brain tumours in children (Laissue et al 2007, Slatkin et al 2009). Bouchet et al (2013) observed that following microbeam irradiation (MBI) of brain tumor bearing rats, the oxygen supply in neoplastic brain tissue was impaired due to vascular radiation damage whereas oxygen supply in normal tissue remained unaffected at equal radiation doses. In this current study, we compared the effects of broad-beam irradiation (BB) and MBI on a normal vascular network using computer simulations to better understand the sparing effect of MRT on normal tissue. For our simulations we developed two computational models: an anatomical model of the microvasculature of the cerebral cortex and a radiation damage model which yields a dose-dependent probability of a blood vessel to remain functional (‘survival probability’)
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