Heavy Ion Minibeam Therapy: Side Effects in Normal Brain

Simple Summary Minibeam therapy spares certain normal tissues compared to conventional radiation therapy. Recently, minibeams applied with protons have shown efficacy in rodent models of glioblastoma. In consideration of translation to human therapy, heavier ions such as helium-4, lithium-7, carbon-12, or oxygen-16 would enable the method to reach deeper into the human brain, potentially sparing greater volumes of normal brain; however, biologic uncertainties and potential toxicities of the method are poorly understood, especially for heavy ions. This work explores the cognitive impairments and pathologic changes seen in normal rodent brain at late timepoints after partial-brain minibeam irradiation with heavy ions. The purpose of this work was to investigate whether minibeam therapy with heavy ions might offer improvements of the therapeutic ratio for the treatment of human brain cancers. To assess neurotoxicity, we irradiated normal juvenile rats using 120 MeV lithium-7 ions at an absorbed integral dose of 20 Gy. Beams were configured either as a solid parallel circular beam or as an array of planar parallel minibeams having 300-micron width and 1-mm center-to-center spacing within a circular array. We followed animals for 6 months after treatment and utilized behavioral testing and immunohistochemical studies to investigate the resulting cognitive impairment and chronic pathologic changes. We found both solid-beam therapy and minibeam therapy to result in cognitive impairment compared with sham controls, with no apparent reduction in neurotoxicity using heavy ion minibeams instead of solid beams under the conditions of this study.