Background/Objectives: Radiation therapy can often lead to structural and functional changes in the brain resulting in radiation-induced brain injury. This study investigates the MRI-detectable effects of whole-brain irradiation across all neuroanatomical structures in adult mice, with a specific focus on T2* MRI measurements, to evaluate regions that may be particularly sensitive to iron accumulation. Methods: One year following irradiation or sham treatment, mice were imaged with a 7T MRI to evaluate changes in regional volume and T2* relaxation times across more than 652 neuroanatomical using the DSURQE mouse brain atlas. Results: Statistical analysis identified 301 altered regions with respect to regional volume and 85 regions with respect to T2* relaxation showing significant differences relative to the control group (p < 0.05). Further data refinement, including the consolidation of redundant, bi-lateral structures revealed 18 subregions with significant changes in both volume and T2*. The data refinement revealed that the most represented system was the olfactory system (8/18 regions, 44%). The olfactory regions also showed the most pronounced changes and greatest correlation between the two metrics. Conclusions: These findings are suggestive that ionizing radiation may cause a pronounced disruption in the olfactory system that coincides with potential iron accumulation.

Nanotechnology has provided considerable advancements in an array of disciplines. Recently, it has been shown that ferumoxytol, a magnetite (Fe₃O₄) nanoparticle, can be oxidized by ionizing radiation. Ferumoxytol nanoparticles have high stability, and thus can be hypothesized that they have dosimetric potential. In this study, it has been observed that xylenol orange, a colorimetric detector of Fe³⁺ used for conventional Fricke dosimetry, was not able to detect radiolytic changes in ferumoxtyol. Electron paramagnetic resonance (EPR) spectroscopy was more readily able to evaluate the oxidation of ferumoxytol. EPR spectroscopy revealed that oxidation of 500 nM ferumoxytol in H₂O was linear up to 20 Gy. This concentration, however, was unable to estimate the delivered dose from a Small Animal Radiation Research Platform system, as a 6 Gy dose was estimated to be 1.37 Gy, which represents a 79.2% underestimation of the dose delivered. Thus, while the high stability of Fe₃O₄ nanoparticles is attractive for use in pre-clinical radiation dosimetry, further radiochemical evaluation may be required before considering them for this application.