Project 1: Deployable Software for the Rapid Assessment of Organ Dose Following Radionuclide Intakes

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PROJECT 1: ABSTRACT This project will develop field-deployable software which, together with external detector measurements, will permit triage-level reporting of organ dose to individuals internally contaminated with radionuclides following Radiological Dispersion Device (RDD), Improvised Nuclear Device (IND), or Nuclear Reactor Accident (NRA) release. These dose estimates will help drive decisions on medical countermeasures and support other forms of exposure assessment such as injury biomarkers. While existing radiological triage software are based on a single pair of 50th percentile adults and a limited array of RDD radionuclides, our software will permit triage screening across a realistic population of adults of varying heights and weights, expansion of this data to include size- variable children and pregnant females, and expansion of the radionuclides considered to include time- dependent fission product mixtures. Our first hypothesis is that a revised series of human anatomic phantoms with detailed models of intra-organ vasculature will permit accurate accounting for circulating blood as an independent source region (important for shorter-lived radionuclides) and will permit realistic estimates of dose to organ parenchyma (important for short-ranged radiations). While these macroscale estimates of organ parenchyma dose are sufficient for in-field radiological triage, this project will additionally perform refined tissue dosimetry as needed for dose-response modeling of organ toxicity. Our second hypothesis is that radionuclide activity is unevenly distributed at the mesoscale (tissue) and microscale (cellular) levels, and thus for short- ranged alpha and beta radiations, there exists a distribution of dose to cell populations to include stem cells, functional subunits, and immunological cells. We will address these hypotheses with the following aims. Aim 1: Model organ-level vasculature within a morphometrically diverse library of computational humans to include adults, children, and pregnant females. Aim 2: Compute radionuclide S values and evaluate detector responses across the entire Aim 1 phantom library. Aim 3: Use the detector responses from Aim 2 and the biokinetic data from Project 2 to design and construct GECAT (the Gamma-Emitter Contamination Assessment Tool). Aim 4: Expand GECAT to include needed radiological triage data for a whole-body scanner designed and validated within Project 2. Aim 5: Develop mesoscale (tissue) and microscale (cell) level mesh-based histology models of the lungs, liver, spleen, and bone marrow, which when coupled to x-ray fluorescent microscopy data from Project 3 (using archived tissues from canine studies of radionuclide inhalation and tissue deposition), will allow us to compute dose distributions to cellular populations that drive radionuclide-induced organ toxicities. This work will be further expanded using XFM data in murine studies of radionuclide inhalation with both pre-exposure and post-exposure administration of a new generation of radionuclide decorporation agents.