Developments in Biodosimetry Methods for Triage With a Focus on X-band Electron Paramagnetic Resonance In Vivo Fingernail Dosimetry

Abstract

Instrumentation and application methodologies for rapidly and accurately estimating individual ionizing radiation dose are needed for on-site triage in a radiological/nuclear event. One such methodology is an in vivo X-band, electron paramagnetic resonance, physically based dosimetry method to directly measure the radiation-induced signal in fingernails. The primary components under development are key instrument features, such as resonators with unique geometries that allow for large sampling volumes but limit radiation-induced signal measurements to the nail plate, and methodological approaches for addressing interfering signals in the nail and for calibrating dose from radiation-induced signal measurements. One resonator development highlighted here is a surface resonator array designed to reduce signal detection losses due to the soft tissues underlying the nail plate. Several surface resonator array geometries, along with ergonomic features to stabilize fingernail placement, have been tested in tissue-equivalent nail models and in vivo nail measurements of healthy volunteers using simulated radiation-induced signals in their fingernails. These studies demonstrated radiation-induced signal detection sensitivities and quantitation limits approaching the clinically relevant range of ≤ 10 Gy. Studies of the capabilities of the current instrument suggest that a reduction in the variability in radiation-induced signal measurements can be obtained with refinements to the surface resonator array and ergonomic features of the human interface to the instrument. Additional studies are required before the quantitative limits of the assay can be determined for triage decisions in a field application of dosimetry. These include expanded in vivo nail studies and associated ex vivo nail studies to provide informed approaches to accommodate for a potential interfering native signal in the nails when calculating the radiation-induced signal from the nail plate spectral measurements and to provide a method for calibrating dose estimates from the radiation-induced signal measurements based on quantifying experiments in patients undergoing total-body irradiation or total-skin electron therapy.

The design of X-band EPR cavity with narrow detection aperture for in vivo fingernail dosimetry after accidental exposure to ionizing radiation

“…Compared with the study of in vivo tooth dosimetry 17,22,28 , the dose assessment precision and limit of the fingernail dosimetry might not be as good as tooth dosimetry (the standard error of prediction was approximately evaluated at 1.5 Gy for L-band spectroscopy of molar teeth) 17,18,28 . However, in vivo fingernail EPR dosimetry has some advantages in the potential for providing information and multiple sites (hands and feet) and future instrumental developments could achieve very competitive convenience for positioning, and speed of measurement 31 .…”

“…The comprehensive dosimetric characteristics of in vivo fingernail EPR measurement still remain a series of further studies in the future work. The strong sensitivity of the radiation-induced signals in fingernails to humidity, especially to the direct contact with water, could result in the large deviation between nominal and EPR doses [29][30][31][32] . This may lead to inapplicability of EPR fingernail dosimetry in some circumstances.…”

Radiation Medical Countermeasures and Use of EPR Biodosimetry to Facilitate Effectiveness of Applied Clinical Procedures

“…Therefore, a biodosimetric assay that could provide this information (regarding IR-dose distribution) would be especially valuable for the rational use and administration of given countermeasures aimed at specific organ systems. In part, this may already be possible with some of the currently available biodosimetric tools; e.g., in vivo EPR dosimetry and the use of nail and tooth samples to assess doses at different regions of the body, or perhaps employing quantitative, real-time molecular assessments of organ-specific genomic or proteomic changes induced by IR exposures [96,99].…”

“…Focusing on the unmet needs related to basic triage procedures and for subsequent application of given medical countermeasures, the in vivo nail dosimetry (as opposed to either in vitro or in vivo tooth/enamel-based dosimetry) approach seems most valuable [96,99], and therefore, we describe it here in more detail, especially as it relates to the potential of the technology to guide the application of any/all post-IR exposure medical procedures. However, as promising as in vivo tooth dosimetry might be, especially for the initial triage for large-scale radiation events, the dosimetric technique is limited, because it provides a dose measurement of a single site on the body (i.e., at the mouth/head).…”

“…By contrast, the less-developed and tested in vivo nail dosimetry assay procedure might ultimately prove to be useful by providing additional IR-dose estimates for multiple, distant body sites. Due to the lower EPR signals in irradiated nails compared to teeth, in vivo nail dosimetry has been developed to take the measurements at a higher frequency than is used for the in vivo analyses of teeth (9.5 GHz for nails versus 1.2 GHz for tooth) [99,101,110]. Nevertheless, it would appear that the 'in vivo EPR biodosimetry of nails' assay has a number of characteristic features that would be valuable for biodosimetry when there is a significant potential for nonhomogeneous exposures.…”