Highly Sensitive Novel Neutron Activation Analysis (NAA) Technology to Quantify Multiple Metals in Human Bone In Vivo

Abstract Metals play a critical role in our health. However, the study of the association between metal exposure/intake and human health has been hampered by a lack of technology to non-invasively quantify body burden of metals. Accurate quantification of metal body burden is important because most of the diseases related to

metal exposures develop over time, and cumulative metal body burden is the best biomarker for individual cumulative metal exposures. Metal body burden is also the most relevant biomarker to determine the toxic threshold of a metal, to evaluate the efficacy of potential treatments of metal-related diseases, and to provide a

method for early diagnose of metal toxicity. Metals cumulates in storage organ such as bone. However, it is challenging to non-invasively detect metals in bone. Our lab has been continuously conducting research in the in vivo quantification of metals and trace elements in human body. In this project, we propose to develop and

validate a highly sensitive working prototype in vivo neutron activation analysis (IVNAA) system to quantify manganese (Mn), sodium (Na), aluminum (Al), potassium (K), and magnesium (Mg) in human bone. The feasibility of the technology has been demonstrated by our preliminary work. In the proposed project, we will

solve the existing technical challenges to meet the sensitivity and reproducibility required for real-world applications, as well as the challenges to extend the technology to broader communities. Monte Carlo (MC) simulations will be used to design an advanced deuterium-deuterium (DD) neutron generator and a highly

efficient U-shaped NaI (Tl) gamma-ray detector, and to design the moderator, fast neutron filter, reflector, and shielding components for the neutron irradiation system, as well as the background reduction component for the gamma-ray detection system. The system will be set up and tested for sensitivity (detection limit) and

reproducibility once the final design is determined. Robust data analysis method and calibration procedures will be developed and tested. We will test the system's sensitivity and reproducibility using bone equivalent phantoms and human cadaver bones, validate the system of measuring multiple metals against ICP-MS, and

improve the design of the system for the comfortability of the human subject and easy operation. We will also apply the system in a small local population to verify utility for human health study applications and sufficient sensitivity and apply the system in a non-local population to verify its ability for wide adoption in human health

studies. The proposed research is expected to result in a valuable tool for the study of relationships between chronic metal exposure and health, nutrition and health, and metal toxicity. It also has great potential to become a clinical tool to diagnose metal toxicity or diseases related to metal exposure and trace element

intake. This R01 proposal is highly responsive to PAR-22-127, Focused Technology Research and Development, with the goal of supporting “the development of technologies with demonstrated proof-of concept that have remaining significant technical challenges to full implementation and broad utility”.