Lead is a ubiquitous toxicant. Bone lead has been established as an important biomarker for cumulative lead exposures and has been correlated with adverse health effects on many systems in the body. K-shell X-ray fluorescence (KXRF) is the standard method for measuring bone lead, but this approach has many difficulties that have limited the widespread use of this exposure assessment method. With recent advancements in X-ray fluorescence (XRF) technology, we have developed a portable system that can quantify lead in bone in vivo within 3 minutes. Our study investigated improvements to the system, four calibration methods, and system validation for in vivo measurements. Our main results show that the detection limit of the system is 2.9 ppm with 2 mm soft tissue thickness, the best calibration method for in vivo measurement is background subtraction, and there is strong correlation between KXRF and portable LXRF bone lead results. Our results indicate that the technology is ready to be used in large human population studies to investigate adverse health effects of lead exposure. The portability of the system and fast measurement time should allow for this technology to greatly advance the research on lead exposure and public/environmental health.

This study was conducted to investigate the methodology and feasibility of developing a portable XRF technology to quantify lead (Pb) in bone in vivo. A portable XRF device was set up and optimal setting of voltage, current, and filter combination for bone lead quantification were selected to achieve the lowest detection limit. The minimum radiation dose delivered to the subject was calculated by Monte Carlo simulations. An ultrasound device was used to measure soft tissue thickness to account for signal attenuation, and an alternative method to obtain soft tissue thickness from the XRF spectrum was developed and shown to be equivalent to the ultrasound measurements (Intraclass Correlation Coefficient, ICC=0.82). We tested the correlation of in vivo bone lead concentrations between the standard KXRF technology and the portable XRF technology. There was a significant correlation between the bone lead concentrations obtained from the standard KXRF technology and those obtained from the portable XRF technology (ICC=0.65). The detection limit for the portable XRF device was about 8.4 ppm with 2 mm soft tissue thickness. The entrance skin dose delivered to the human subject was about 13 mSv and the total body effective dose was about 1.5 μSv and should pose a minimal radiation risk. In conclusion, portable XRF technology can be used for in vivo bone lead measurement with sensitivity comparable to the KXRF technology and good correlation with KXRF measurements.

Childhood lead (Pb) poisoning remains a global issue, especially in industrial areas. In this study, 115 children with average age 5.7 years were recruited as either patient diagnosed with Pb poisoning or controls at Xinhua Hospital in China. The subjects’ bone Pb was measured with a K-shell X-ray fluorescence (KXRF) and a portable X-ray fluorescence (XRF) system. A significant correlation between KXRF bone Pb and blood Pb and portable XRF and KXRF measurements were observed. The half-life of blood-lead was calculated to be 9.96 ± 3.92 d. Our results indicate that bone is a useful biomarker for Pb in children.

Objective Bone lead is a cumulative measure of lead exposure that can also be remobilized. We examined repeated measures of bone lead over 11 years to characterize long-term changes and identify predictors of tibia and patella lead stores in an elderly male population. Methods Lead was measured every 3–5 years by k-x-ray fluorescence and mixed-effect models with random effects were used to evaluate change over time. Results 554 participants provided up to 4 bone lead measurements. Final models predicted a −1.4% annual decline (95%CI: −2.2,−0.7) for tibia lead and piecewise linear model for patella with an initial decline of 5.1% per year (95%CI: −6.2,−3.9) during the first 4.6 years but no significant change thereafter (−0.4% (95% CI: −2.4, 1.7)). Conclusions These results suggest that bone lead half-life may be longer than previously reported.

Literature data indicate that bone is a major storage organ for manganese (Mn), accounting for 43% of total body Mn. However, the kinetic nature of Mn in bone, especially the half-life (t1/2), remained unknown. This study was designed to understand the time-dependence of Mn distribution in rat bone after chronic oral exposure. Adult male rats received 50 mg Mn/kg (as MnCl2) by oral gavage, 5 days per week, for up to 10 weeks. Animals were sacrificed every two weeks during Mn administration for the uptake study, and on day 1, week 2, 4, 8, or 12 after the cessation at 6-week Mn exposure for the t1/2 study. Mn concentrations in bone (MnBn) were determined by AAS analysis. By the end of 6-week’s treatment, MnBn appeared to reach the steady state (Tss) level, about 2–3.2 fold higher than MnBn at day 0. Kinetic calculation revealed t1/2s of Mn in femur, tibia, and humerus bone of 77 (r=0.978), 263 (r=0.988), and 429 (r=0.994) days, respectively; the average t1/2 in rat skeleton was about 143 days, equivalent to 8.5 years in human bone. Moreover, MnBn were correlated with Mn levels in striatum, hippocampus, and CSF. These data support MnBn to be a useful biomarker of Mn exposure.

A deuterium-deuterium (DD) neutron generator–based neutron activation analysis (NAA) system has been developed to quantify metals, including manganese (Mn), in bone in vivo. A DD neutron generator with a flux of up to 3*109 neutrons/second was set up in our lab for this purpose. Optimized settings, including moderator, reflector, and shielding material and thickness, were selected based on Monte Carlo (MC) simulations conducted in our previous work. Hand phantoms doped with different Mn concentrations were irradiated using the optimized DD neutron generator irradiation system. The Mn characteristic γ-rays were collected by an HPGe detector system with 100% relative efficiency. The calibration line of the Mn/calcium (Ca) count ratio versus bone Mn concentration was obtained (R2 = 0.99) using the hand phantoms. The detection limit (DL) was calculated to be about 1.05 μg/g dry bone (ppm) with an equivalent dose of 85.4 mSv to the hand. The DL can be reduced to 0.74 ppm by using two 100% HPGe detectors. The whole body effective dose delivered to the irradiated subject was calculated to be about 17 μSv. Given the average normal bone Mn concentration of 1 ppm in the general population, this system is promising for in vivo bone Mn quantification in humans.

This study was conducted to investigate the methodology and feasibility of developing a transportable neutron activation analysis (NAA) system to quantify manganese (Mn) in bone using a portable deuterium–deuterium (DD) neutron generator as the neutron source. Since a DD neutron generator was not available in our laboratory, a deuterium–tritium (DT) neutron generator was used to obtain experimental data and validate the results from Monte Carlo (MC) simulations. After validation, MC simulations using a DD generator as the neutron source were then conducted. Different types of moderators and reflectors were simulated, and the optimal thicknesses for the moderator and reflector were determined. To estimate the detection limit (DL) of the system, and to observe the interference of the magnesium (Mg) γ line at 844 keV to the Mn γ line at 847 keV, three hand phantoms with Mn concentrations of 30 parts per million (ppm), 150 ppm, and 500 ppm were made and irradiated by the DT generator system. The Mn signals in these phantoms were then measured using a 50% high-efficiency high-purity germanium (HPGe) detector. The DL was calculated to be about 4.4 ppm for the chosen irradiation, decay, and measurement time. This was calculated to be equivalent to a DL of about 3.3 ppm for the DD generator system. To achieve this DL with one 50% high-efficiency HPGe detector, the dose to the hand was simulated to be about 37 mSv, with the total body equivalent dose being about 23μSv. In conclusion, it is feasible to develop a transportable NAA system to quantify Mn in bone in vivo with an acceptable radiation exposure to the subject.

Background Higher long-term cumulative lead exposure predicts faster cognitive decline in older men, but evidence of an association in women is lacking. Objective To determine if there is an association between lead exposure and cognitive decline in women. Methods This study considers a sample of 584 women from the Nurses’ Health Study who live in or near Boston, Massachusetts. We quantified lead exposure using biomarkers of lead exposure assessed in 1993–2004 and evaluated cognitive decline by repeated performance on a telephone battery of cognitive tests primarily assessing learning, memory, executive function, and attention completed in 1995–2008. All cognitive test scores were z-transformed for use in analyses. We used linear mixed models with random effects to quantify the association between each lead biomarker and change in cognition overall and on each individual test. Results Consideration of individual tests showed greater cognitive decline with increased tibia lead concentrations, a measure of long-term cumulative exposure, for story memory and category fluency. The estimated excess annual decline in overall cognitive test z-score per SD increase in tibia bone lead concentration was suggestive, although the confidence intervals included the null (0.024 standard units, 95% confidence interval: −0.053 , 0.004 – an additional decline in function equivalent to being 0.33 years older). We found little support for associations between cognitive decline and patella or blood lead, which provide integrated measures of exposure over shorter timeframes. Conclusions Long-term cumulative lead exposure may be weakly associated with faster cognitive decline in community-dwelling women, at least in some cognitive domains.