Microdosimetry in space: a systematic analysis of the μD dose-response model components for exposures to low to moderate doses of heavy Ions

A microdosimetric-based (μD) dose-response model was recently proposed linking microdosimetry quantities to endpoints related to carcinogenesis for exposures relevant to the space radiation environment. In the μD model, the biological response to radiation is assumed to solely arise from microscopic spherical targets that received energy, which can be divided into: (1) targets not traversed by ions but that have received energy from δ-electrons of distant tracks (unhit irradiated targets), (2) targets traversed by one ion (singly hit targets), and (3) targets traversed by multiple tracks (multiply hit targets). The μD dose-response model was initially calibrated and validated using three experimental datasets, establishing its applicability and usefulness for exposures and biological endpoints of interest to space radiation induced carcinogenesis. Here, the μD dose-response model is used to study the global behavior of the three model components as a function of macroscopic absorbed dose, radiation quality, and spherical target size – major parameters influencing space radiation induced biological effects. Specifically, this work analyzes the effects of total macroscopic absorbed dose (10 –4 Gy to 2 Gy), radiation quality (kinetic energy in the range 50 MeV/n to 5000 MeV/n, ion charge in the range 6 to 41, linear energy transfer (LET) > 10 keV/μm), and target size (2.76 μm to 10 μm) on the key components of the μD dose-response model for each of the irradiated subpopulations of cells: specific energy distribution, subpopulation fraction, mean specific energy, and mean target population dose. In the μD dose-response model, this latter quantity is directly related to the biological outcome. It is found that the total mean target dose is dominated by singly hit targets at low macroscopic doses and by multiply-hit targets at higher macroscopic doses, while the contribution of unhit irradiated targets is marginal. Overall, the trends of the analyzed microdosimetric quantities are driven by differences in track structure and fluences between low- and high-LET ions, for equal macroscopic doses. Identical quantities are found when dose-related quantities (beam dose, specific energy distribution, mean specific energy and mean target population dose) are scaled with the square of the radius. Establishing the global behavior of these μD dose-response model components for space radiation exposures will support future advancements of the μD model and subsequent understanding of radiation quality.