Public Abstract

DE-SC0025487: Combined Dosimetric and Toxicological Contributions to Bone Marrow Response in Mice from Low-Dose Strontium Exposure using AI-Driven Mouse Model and Digital Twins

Award Status: Active

Institution: University of Florida, Gainesville, FL
UEI: NNFQH1JAPEP3
DUNS: 969663814

Most Recent Award Date: 08/28/2024
Number of Support Periods: 1
PM: Kulkarni, Resham

Current Budget Period: 09/01/2024 - 08/31/2025
Current Project Period: 09/01/2024 - 08/31/2027
PI: Bolch, Wesley

Supplement Budget Period: N/A

Public Abstract

In this proposed collaboration between the University of Florida (UF), the Georgia Institute of Technology (GT), and the US Department of Energy Lawrence Berkeley National Laboratory (LBNL), we will investigate molecular markers for bone marrow dose-response to low-LET, low-dose, and low-dose rate irradiation of the marrow tissues in a mouse model for intravenous intra-tracheal installation of stable and radioactive strontium. Internalized radionuclides constitute a significant pathway by which humans are exposed to low-LET ionizing radiation at low doses and at low dose-rates. These exposures include environmental and occupational radionuclide scenarios, but additionally include the use of diagnostic nuclear medicine for cancer detection and treatment monitoring. In the vast majority of radiation response-modeling studies, the laboratory mouse is exposed to external beams of radiation whether whole or partial body. As such, tissue dosimetry in these study populations may be readily assessed through beam energy and intensity characterization coupled to standardized depth-dose profiles. For internalized radionuclide exposures, tissue dosimetry is much more complex and must invoke anatomic computational models of the laboratory mouse for organ self-dose and cross-dose radiation transport simulations, coupled with time-dependent biokinetic models of radionuclide airway, blood, and tissue radionuclide parent and progeny transport. In this proposed series of studies, we will significantly enhance computational tools for internal radionuclide dosimetry in the laboratory mouse including the use of artificial intelligence (AI) across all tasks. This enhanced computational tool will be made available throughout the low-dose radiation research community. The enhanced anatomic and physiological mouse computational phantom will be utilized in this study to further enhance dose-response modeling to low-dose bone marrow irradiation via radiostrontium inhalation studies at LBNL to determine the biomarker expression attributable to the toxicological versus radiological component of internal emitters. We further note that the 2022 National Academies Report (Table S.1) recommends elucidation of biological localization of internalized radionuclides; measurements of radiation-induced damage and response mechanisms; development of high-fidelity anatomically/physiologically based dosimetry; and development of modern statistical/computational methods for dose reconstruction (priorities B1, B2, I3). In this research proposal, we will explicitly address each report recommendation in the project scope.

In this proposed collaboration between the University of Florida (UF), the Georgia Institute of Technology (GT), and the US Department of Energy Lawrence Berkeley National Laboratory (LBNL), we will investigate molecular markers for bone marrow dose-response to low-LET, low-dose, and low-dose rate irradiation of the marrow tissues in a mouse model for intravenous intra-tracheal installation of stable and radioactive strontium. Internalized radionuclides constitute a significant pathway by which humans are exposed to low-LET ionizing radiation at low doses and at low dose-rates. These exposures include environmental and occupational radionuclide scenarios, but additionally include the use of diagnostic nuclear medicine for cancer detection and treatment monitoring. In the vast majority of radiation response-modeling studies, the laboratory mouse is exposed to external beams of radiation whether whole or partial body. As such, tissue dosimetry in these study populations may be readily assessed through beam energy and intensity characterization coupled to standardized depth-dose profiles. For internalized radionuclide exposures, tissue dosimetry is much more complex and must invoke anatomic computational models of the laboratory mouse for organ self-dose and cross-dose radiation transport simulations, coupled with time-dependent biokinetic models of radionuclide airway, blood, and tissue radionuclide parent and progeny transport. In this proposed series of studies, we will significantly enhance computational tools for internal radionuclide dosimetry in the laboratory mouse including the use of artificial intelligence (AI) across all tasks. This enhanced computational tool will be made available throughout the low-dose radiation research community. The enhanced anatomic and physiological mouse computational phantom will be utilized in this study to further enhance dose-response modeling to low-dose bone marrow irradiation via radiostrontium inhalation studies at LBNL to determine the biomarker expression attributable to the toxicological versus radiological component of internal emitters. We further note that the 2022 National Academies Report (Table S.1) recommends elucidation of biological localization of internalized radionuclides; measurements of radiation-induced damage and response mechanisms; development of high-fidelity anatomically/physiologically based dosimetry; and development of modern statistical/computational methods for dose reconstruction (priorities B1, B2, I3). In this research proposal, we will explicitly address each report recommendation in the project scope.