title: Sparing of tissue by using micro-slit-beam radiation therapy reduces neurotoxicity compared with broad-beam radiation therapy.
abstract: Micro-slit-beam radiation therapy (MRT) using synchrotron-generated X-ray beams allows for extremely high-dose irradiation. However, the toxicity of MRT in central nervous system (CNS) use is still unknown. To gather baseline toxicological data, we evaluated mortality in normal mice following CNS-targeted MRT. Male C57BL/6 J mice were head-fixed in a stereotaxic frame. Synchrotron X-ray-beam radiation was provided by the SPring-8 BL28B2 beam-line. For MRT, radiation was delivered to groups of mice in a 10 × 12 mm unidirectional array consisting of 25-μm-wide beams spaced 100, 200 or 300 μm apart; another group of mice received the equivalent broad-beam radiation therapy (BRT) for comparison. Peak and valley dose rates of the MRT were 120 and 0.7 Gy/s, respectively. Delivered doses were 96-960 Gy for MRT, and 24-120 Gy for BRT. Mortality was monitored for 90 days post-irradiation. Brain tissue was stained using hematoxylin and eosin to evaluate neural structure. Demyelination was evaluated by Klüver-Barrera staining. The LD50and LD100when using MRT were 600 Gy and 720 Gy, respectively, and when using BRT they were 80 Gy and 96 Gy, respectively. In MRT, mortality decreased as the center-to-center beam spacing increased from 100 μm to 300 μm. Cortical architecture was well preserved in MRT, whereas BRT induced various degrees of cerebral hemorrhage and demyelination. MRT was able to deliver extremely high doses of radiation, while still minimizing neuronal death. The valley doses, influenced by beam spacing and irradiated dose, could represent important survival factors for MRT.
authors.affiliation: Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuouku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Naritoshi
authors.initials: N
authors.lastname: Mukumoto
authors.affiliation: Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuouku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuouku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Akasaka
authors.affiliation: Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuouku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Shimizu
authors.affiliation: Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuouku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Osuga
authors.affiliation: Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuouku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Miyawaki
authors.affiliation: Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuouku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuouku, Kobe, Hyogo, 650-0017, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ejima
authors.affiliation: Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences, Kobe, Hyogo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miura
authors.affiliation: Japan Synchrotron Radiation Research Institute, Sayo, Hyogo, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Umetani
authors.affiliation: Department of Neurosurgery, Shinsuma Hospital, Kobe, Hyogo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kondoh
authors.affiliation: Division of Radiation Oncology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuouku, Kobe, Hyogo, 650-0017, Japan rsasaki@med.kobe-u.ac.jp.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D003711:Demyelinating Diseases / Q000473:pathology; D004307:Dose-Response Relationship, Radiation; D053208:Kaplan-Meier Estimate; D008297:Male; D008810:Mice, Inbred C57BL; D009420:Nervous System / Q000528:radiation effects*; D059351:Organ Sparing Treatments; D011878:Radiotherapy; D016019:Survival Analysis
keywords: microbeam; neurotoxicity; radiation therapy; slit beam; synchrotron radiation