title: Irradiation of Neurons with High-Energy Charged Particles: An In Silico Modeling Approach.
abstract: In this work, a stochastic computational model of microscopic energy deposition events is used to study for the first time damage to irradiated neuronal cells of the mouse hippocampus. An extensive library of radiation tracks for different particle types is created to score energy deposition in small voxels and volume segments describing a neuron's morphology that later are sampled for given particle fluence or dose. Methods included the construction of in silico mouse hippocampal granule cells from neuromorpho.org with spine and filopodia segments stochastically distributed along the dendritic branches. The model is tested with high-energy (56)Fe, (12)C, and (1)H particles and electrons. Results indicate that the tree-like structure of the neuronal morphology and the microscopic dose deposition of distinct particles may lead to different outcomes when cellular injury is assessed, leading to differences in structural damage for the same absorbed dose. The significance of the microscopic dose in neuron components is to introduce specific local and global modes of cellular injury that likely contribute to spine, filopodia, and dendrite pruning, impacting cognition and possibly the collapse of the neuron. Results show that the heterogeneity of heavy particle tracks at low doses, compared to the more uniform dose distribution of electrons, juxtaposed with neuron morphology make it necessary to model the spatial dose painting for specific neuronal components. Going forward, this work can directly support the development of biophysical models of the modifications of spine and dendritic morphology observed after low dose charged particle irradiation by providing accurate descriptions of the underlying physical insults to complex neuron structures at the nano-meter scale.
authors.affiliation: Department of Health Physics and Diagnostic Sciences, University of Nevada, Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Murat
authors.initials: M
authors.lastname: Alp
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Vipan K
authors.initials: VK
authors.lastname: Parihar
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, Irvine, California, United States of America.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Limoli
authors.affiliation: Department of Health Physics and Diagnostic Sciences, University of Nevada, Las Vegas, Las Vegas, Nevada, United States of America.
authors.forename: Francis A
authors.initials: FA
authors.lastname: Cucinotta
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D003712:Dendrites / Q000528:radiation effects; D018891:Dentate Gyrus / Q000166:cytology; D051379:Mice; D008959:Models, Neurological; D009010:Monte Carlo Method; D009474:Neurons / Q000528:radiation effects*; D011554:Pseudopodia / Q000528:radiation effects; D011854:Radiochemistry; D011874:Radiometry / Q000379:methods*