The feasibility of K XRF bone lead measurements in mice assessed using 3D-printed phantoms

This article describes the development of a system forin vivomeasurements of lead body burden in mice using¹⁰⁹Cd K x-ray fluorescence (XRF). This K XRF system could facilitate early-stage studies on interventions that ameliorate or reverse organ tissue damage from lead poisoning by reducing animal numbers through a cross-sectional study approach. A novel mouse phantom was developed based on a mouse atlas and 3D-printed using PLA plastic with plaster of Paris 'bone' inserts. PLA plastic was found to be a good surrogate for soft tissue in XRF measurements and the phantoms were found to be good models of mice. As expected, lead detection limits varied with mouse size, mouse orientation, and mouse position with respect to the source and detector. The work suggests that detection limits of 10 to 20μg Pb per g bone mineral may be possible for a 2 to 3 hour XRF measurement in a single animal, an adequate limit for some pre-clinical studies. The¹⁰⁹Cd K XRF mouse measurement system was also modeled using the Monte Carlo code MCNP. The combination of experiment and modeling found that contrary to expectation, accurate measurements of lead levels in mice required calibration using mouse-specific calibration standards due to the coherent scatter peak normalization failing when small animals are measured. MCNP modeling determined that this was because the coherent scatter signal from soft tissue, which until now has been assumed negligible, becomes significant when compared to the coherent scatter signal in bone in small animals. This may have implications for some human measurements. This work suggests that¹⁰⁹Cd K x-ray fluorescence measurements of lead body burden are precise enough to make the system feasible for small animals if appropriately calibrated. Further work to validate the technology's measurement accuracy and performancein vivowill be required.