Long-Term, Non-Invasive Detection of Low-Dose Ionizing Radiation Exposure

Abstract

Ionizing radiation induces complex changes in cells and tissues. The conventional approach to biological dosimetry has been to integrate physical and clinical measurements to optimize dose assessment. Molecular biodosimetry is an effective strategy to monitor radiation exposure and hematologic, cytogenetic, protein and transcript-based approaches have been developed to increase dose estimation accuracy. However, these approaches are invasive, time-consuming, have limited effectiveness over time, and importantly do not accurately inform on low dose radiation exposures. Therefore, novel, non-invasive, biomarkers are required that can overcome these limitations. We developed a pipeline that employs Fourier transform infrared (FTIR) spectroscopy in the mid-infrared spectrum to identify a signature of low dose ionizing radiation exposure in mouse ear pinnae over time. Two cohorts of C57BL/6J and one cohort of BALB/c mice were followed for ninety days after total body X-ray exposures of 10, 50, 100 or 200 cGy. The stratum corneum layer of the ear pinnae were repeatedly measured with attenuated total reflectance - focal plane array (ATR-FPA)-FTIR at 5, 14, 21, 49 and 90 days after radiation exposure. We found statistically significant discriminative power for all doses and all tested time-points out to 90 days after exposure. Classification accuracy was maximized when testing 14 days after exposure (specificity > 0.9 with a sensitivity threshold of 0.9) and dropped by roughly 30% sensitivity at 90 days. Since only hundreds of samples were required to learn highly discriminative signatures, developing human-relevant diagnostic capabilities is likely feasible and this non-invasive procedure points toward future non-invasive biodosimetry applications at population scales.