Mercury and selenium distribution in human brain tissue using synchrotron micro-X-ray fluorescence.

Mercury is a well-recognized environmental contaminant and neurotoxin, having been associated with a number of deleterious neurological conditions including neurodegenerative diseases, such as Alzheimer's disease. To investigate how mercury and other metals behave in the brain, we used synchrotron micro-X-ray fluorescence to map the distribution pattern and quantify concentrations of metals in human brain. Brain tissue was provided by the Rush Alzheimer's Disease Center and samples originated from individuals diagnosed with Alzheimer's disease and without cognitive impairment. Data were collected at the 2-ID-E beamline at the Advanced Photon Source at Argonne National Laboratory with an incident beam energy of 13 keV. Course scans were performed at low resolution to determine gross tissue features, after which smaller regions were selected to image at higher resolution. The findings revealed (1) the existence of mercury particles in the brain samples of two subjects; (2) co-localization and linear correlation of mercury and selenium in all particles; (3) co-localization of these particles with zinc structures; and (4) association with sulfur in some of these particles. These results suggest that selenium and sulfur may play protective roles against mercury in the brain, potentially binding with the metal to reduce the induced toxicity, although at different affinities. Our findings call for further studies to investigate the relationship between mercury, selenium, and sulfur, as well as the potential implications in Alzheimer's disease and related dementias.

In vivo quantification of strontium in bone among adults using portable x-ray fluorescence.

BACKGROUND AND OBJECTIVE: Bone strontium (Sr) is a reliable biomarker for studying related bone health outcomes and the effectiveness of Sr supplements in osteoporosis disease treatment. In this study, we evaluated the sensitivity of portable x-ray fluorescence (XRF) technology for in vivo bone Sr quantification among adults. MATERIALS AND METHODS: Sr-doped bone-equivalent phantoms were used for system calibration. Using the portable XRF, we measured bone Sr levels in vivo in mid-tibia bone in 76 adults, 38-95 years of age, living in Indiana, US; we also analyzed bone data of 29 adults, 53-82 years of age, living in Shanghai, China. The same portable XRF device and system settings were used in measuring their mid-tibia bone. We compared bone Sr concentrations by sex, age, and recruitment site. We also used multiple linear regression model to estimate the association of age with bone Sr concentration, adjusting for sex and recruitment site. RESULTS: The uncertainty of in vivo individual measurement increased with higher soft tissue thickness overlying bone, and it ranged from 1.0 ug/g dry bone (ppm) to 2.4 ppm with thickness ranging from 2 to 7 mm, with a measurement time of 5 min. Geometric mean (95% confidence interval (CI)) of the bone Sr concentration was 79.1 (70.1, 89.3) ppm. After adjustment for recruitment site and sex, an increase in five years of age was associated with a 8.9% (95% CI: 2.5%, 15.6%) increase in geometric mean bone Sr concentration. DISCUSSION AND CONCLUSION: Sr concentrations were consistently well above detection limits of the portable XRF, and exhibited an expected increase with age. These data suggest that the portable XRF can be a valuable technology to quantify Sr concentration in bone, and in the study of Sr-related health outcomes among adults, such as bone mineral density (BMD) and bone fracture risk.

Validation of in vivo toenail measurements of manganese and mercury using a portable X-ray fluorescence device.

BACKGROUND AND OBJECTIVE: Toenail metal concentrations can be used as an effective biomarker for exposure to environmental toxicants. Typically toenail clippings are measured ex vivo using inductively coupled plasma mass spectrometry (ICP-MS). X-ray fluorescence (XRF) toenail metal measurements done on intact toenails in vivo could be used as an alternative to alleviate some of the disadvantages of ICP-MS. In this study, we assessed the ability to use XRF to measure toenail metal concentrations in real-time without having to clip the toenails (i.e., in vivo) in two occupational settings for exposure assessment of manganese and mercury. MATERIALS AND METHODS: The portable XRF method used a 3-min in vivo measurement of toenails prior to clipping and was assessed against ICP-MS measurement of toenail clippings taken immediately after the XRF measurement and work history for a group of welders (n = 16) assessed for manganese exposure and nail salon workers (n = 10) assessed for mercury exposure. RESULTS AND CONCLUSIONS: We identified that in vivo XRF metal measurements were able to discern exposure to manganese in welders and mercury in nail salon workers. We identified significant positive correlations between ICP-MS of clippings and in vivo XRF measures of both toenail manganese (R = 0.59, p = 0.02) and mercury (R = 0.74, p < 0.001), as well as between in vivo XRF toenail manganese and work history among the welders (R = 0.55, p = 0.03). We identified in vivo XRF detection limits to be 0.5 µg/g for mercury and 2.6 µg/g for manganese. Further work should elucidate differences in the timing of exposure using the in vivo XRF method over toenail clippings and modification of measurement time and x-ray setting to further decrease the detection limit. In vivo portable, XRF measurements can be used to effectively measure toenail Mn and Hg in occupational participants in real-time during study visits and at a fraction of the cost.

The association of bone and blood manganese with motor function in Chinese workers.

Manganese (Mn) is an essential element. However, Mn overexposure is associated with motor dysfunction. This cross-sectional study assessed the association between bone Mn (BnMn) and whole blood Mn (BMn) with motor function in 59 Chinese workers. BnMn and BMn were measured using a transportable in vivo neutron activation analysis system and inductively coupled plasma mass spectrometry, respectively. Motor function (manual coordination, postural sway, postural hand tremor, and fine motor function) was assessed using the Coordination Ability Test System (CATSYS) and the Purdue Pegboard. Relationships between Mn biomarkers and motor test scores were analyzed with linear regression models adjusted for age, education, current employment, and current alcohol consumption. BMn was significantly inversely associated with hand tremor intensity (dominant hand (ß=-0.04, 95 % confidence interval (CI):-0.07, -0.01; non-dominant hand ß=-0.05, 95 % CI:-0.08, -0.01) hand tremor center frequency (non-dominant hand ß=-1.61, 95 % CI:-3.03, -0.19) and positively associated with the Purdue Pegboard Assembly Score (ß = 4.58, 95 % CI:1.08, 8.07). BnMn was significantly inversely associated with finger-tapping performance (non-dominant hand ß=-0.02, 95 % CI:-0.04,-0.004), mean sway (eyes closed and foam ß=-0.68, 95 % CI:-1.31,-0.04), and positively associated with hand tremor center frequency (dominant hand, ß = 0.40, 95 % CI:0.002, 0.80). These results suggest BMn is related to better postural hand tremor and fine motor control and BnMn is related to worse motor coordination and postural hand tremor but better (i.e., less) postural sway. The unexpected positive results might be explained by choice of biomarker or confounding by work-related motor activities. Larger, longitudinal studies in this area are recommended.

Distribution of Pb and Se in mouse brain following subchronic Pb exposure by using synchrotron X-ray fluorescence.

Lead (Pb) is a well-known neurotoxicant and environmental hazard. Recent experimental evidence has linked Pb exposure with neurological deterioration leading to neurodegenerative diseases, such as Alzheimer's disease. To understand brain regional distribution of Pb and its interaction with other metal ions, we used synchrotron micro-x-ray fluorescence technique (µ-XRF) to map the metal distribution pattern and to quantify metal concentrations in mouse brains. Lead-exposed mice received oral gavage of Pb acetate once daily for 4 weeks; the control mice received sodium acetate. Brain tissues were cut into slices and subjected for analysis. Synchrotron µ-XRF scans were run on the PETRA III P06 beamline (DESY). Coarse scans of the entire brain were performed to locate the cortex and hippocampus, after which scans with higher resolution were run in these areas. The results showed that: a) the total Pb intensity in Pb-exposed brain slices was significantly higher than in control brain; b) Pb typically deposited in localized particles of <10 um2 in both the Pb-exposed and control brain slices, with more of these particles in Pb-exposed samples; c) selenium (Se) was significantly correlated with Pb in these particles in the cortex and hippocampus/corpus callosum regions in the Pb-exposed samples, and the molar ratio of the Se and Pb in these particles is close to 1:1. These results indicated that Se may play a crucial role in Pb-induced neurotoxicity. Our findings call for further studies to investigate the relationship between Pb exposure and possible Se detoxification responses, and the implication in the etiology of Alzheimer's disease.

Rodent hair is a Poor biomarker for internal manganese exposure.

Hair is used as a biomarker of manganese (Mn) exposure, yet there is limited evidence to support its utility to quantify internal vs external Mn exposure. C57BL/6 J mice and Sprague-Dawley rats were exposed in two blocks of 3 subcutaneous injections every 3 days starting on day 0 or 20. The control group received two blocks of saline (vehicle); Treatment A received the first block as Mn (50 mg/kg MnCl2 tetrahydrate), with the second block as either methylmercury (MeHg at 2.6 or 1.3 mg/kg) for mice or vehicle for rats; and Treatment B received Mn for both blocks. Hair was collected on days 0 and 60 from all treatment groups and Mn quantified by inductively coupled plasma-mass spectrometry (ICP-MS) and total Hg by Direct Mercury Analyzer (DMA). No correlation between internal Mn dose and hair Mn was observed, whereas hair Hg was significantly elevated in MeHg exposed vs non-exposed mice. Whole body Mn content at day 60 was quantified postmortem by neutron activation analysis, which detected significantly elevated Mn for Treatment B in mice and rats. Overall, we find no evidence to support the use of hair as a valid biomarker for internal exposure to Mn at a neurotoxic level.

Whole body potassium as a biomarker for potassium uptake using a mouse model.

Potassium is known for its effect on modifiable chronic diseases like hypertension, cardiac disease, diabetes (type-2), and bone health. In this study, a new method, neutron generator based neutron activation analysis (NAA), was utilized to measure potassium (K) in mouse carcasses. A DD110 neutron generator based NAA assembly was used for irradiation.Thirty-two postmortem mice (n= 16 males and 16 females, average weight [Formula: see text] and [Formula: see text] g) were employed for this study. Soft-tissue equivalent mouse phantoms were prepared for the calibration. All mice were irradiated for 10 minutes, and the gamma spectrum with 42K was collected using a high efficiency, high purity germanium (HPGe) detector. A lead shielding assembly was designed and developed around the HPGe detector to obtain an improved detection limit. Each mouse sample was irradiated and measured twice to reduce uncertainty. The average potassium concentration was found to be significantly higher in males [Formula: see text] compared to females [Formula: see text]. We also observed a significant correlation between potassium concentration and the weight of the mice. The detection limit for potassium quantification with the NAA system was 46 ppm. The radiation dose to the mouse was approximately 56 [Formula: see text] mSv for 10-min irradiation. In conclusion, this method is suitable for estimating individual potassium concentration in small animals. The direct evaluation of total body potassium in small animals provides a new way to estimate potassium uptake in animal models. This method can be adapted later to quantify potassium in the human hand and small animals in vivo. When used in vivo, it is also expected to be a valuable tool for longitudinal assessment, kinetics, and health outcomes.

Blood DNA methylation biomarkers of cumulative lead exposure in adults.

BACKGROUND: Lead is a ubiquitous toxicant following three compartment kinetics with the longest half-life found in bones. Patella and tibia lead levels-validated measures of cumulative exposure-require specialized X-ray-fluorescence-spectroscopy available only in a few centers worldwide. We developed minimally invasive biomarkers reflecting individual cumulative lead exposure using blood DNA methylation profiles-obtainable via Illumina 450K or IlluminaEPIC bead-chip assays. METHODS: We developed and tested two methylation-based biomarkers from 348 Normative Aging Study (NAS) elderly men. We selected methylation sites with strong associations with bone lead levels via robust regressions analysis and constructed the biomarkers using elastic nets. Results were validated in a NAS subset, reporting specificity, and sensitivity. FINDINGS: Participants were 73 years old on average (standard deviation, SD = 6), with moderate lead levels of (mean ± SD patella: 27 ± 18 µg/g; tibia:21 ± 13 µg/g). Methylation-based biomarkers for lead in patella and tibia included 59 and 138 DNA methylation sites, respectively. Estimated lead levels were significantly correlated with actual measured values, (r = 0.62 patella, r = 0.59 tibia) and had low mean square error (MSE) (MSE = 0.68 patella, MSE = 0.53 tibia). Means and distributions of the estimated and actual lead levels were not significantly different across patella and tibia bones (p > 0.05). Methylation-based biomarkers discriminated participants highly exposed (>median) to lead with a specificity of 74 and 73% for patella and tibia lead levels, respectively, with 70% sensitivity. INTERPRETATION: DNA methylation-based lead biomarkers are novel tools that can be used to reconstruct decades' worth of individual cumulative lead exposure using only blood DNA methylation profiles and may help identify the consequences of cumulative exposure.

Evaluation of a portable XRF device for in vivo quantification of lead in bone among a US population.

BACKGROUND: Lead (Pb) concentration in bone is a reliable biomarker for cumulative Pb exposure and studying associated health outcomes. However, the standard K-shell fluorescence (KXRF) bone Pb measurement technology has limitations in large-scale population studies. OBJECTIVE: We compared measurements from a portable XRF device and a KXRF device. METHODS: We measured bone Pb concentrations in vivo using portable XRF and KXRF, each measured at the mid-tibia bone in 71 people, 38-95 years of age (mean ± SD = 63 ± 11 years) living in or near three Indiana communities, US; 10 participants were occupationally exposed. We estimated the correlation between bone Pb concentrations measured by both devices. We also examined the extent to which the detection limit (DL) of the portable XRF was influenced by scan time and overlying soft tissue thickness. Finally, we quantified the associations of estimated bone Pb concentration with age and age with soft tissue thickness. RESULTS: The mean bone Pb concentration measured via portable XRF was 12.3 ± 16.7 mg Pb/kg dry bone. The uncertainty of a 3-minute (N = 60) in vivo portable XRF measurement ranged from 1.8 to 6.3 mg/kg, in the context of soft tissue thickness ranging from 2 to 6 mm. This uncertainty was reduced by a factor of 1.4 with 5-minute measurements (N = 11). Bone Pb measurements via portable XRF and KXRF were significantly correlated: r = 0.48 for all participants, and r = 0.73 among participants with soft tissue thickness < 6 mm (72% of the sample). Bone Pb concentrations were higher among participants who were older or were occupationally exposed to Pb. Soft tissue thickness decreased with age. CONCLUSION: With its ease of use, portability, and comparable sensitivity with conventional KXRF systems, the portable XRF could be a valuable tool for non-invasive quantification of bone Pb in vivo, especially for people with thinner soft tissue.

In vivoneutron activation assembly design for quantification of trace elements using MCNP.

Background: Trace and essential elements both play a crucial role in maintaining normal cellular and organ functions in human, while abnormal exposure to some of them is also potentially related to diseases, e.g.manganism. To study the association between elemental intake and health outcomes, accurate assessment of elemental uptake and storage in the human body is essential.Objective: Technology based on neutron activation analysis can be used forin vivomeasurement of the trace elements given that the measurement system guarantees a low detection limit with an acceptable dose. This study aims to design and optimize a customized and portable deuterium-deuterium neutron generator-based irradiation assembly for the NAA of trace elementsin vivo,using Monte Carlo simulations.Approach: The irradiation assembly includes a moderator, a fast neutron filter, a reflector, and shielding. The human hand phantoms doped with manganese (Mn) and potassium (K) are used to determine the respective elements' system sensitivity and detection limit.Main results: The calculated detection limit is 0.16µg Mn per gram dry bone (ppm) for Mn and 17 ppm for K, with an equivalent dose of 36 mSv to the hand for 10 min irradiation.Significance: This more sensitivein vivoneutron activation analysis system will detect trace elementsin vivo.

Characterization of bone aluminum, a potential biomarker of cumulative exposure, within an occupational population from Zunyi, China.

OBJECTIVES: Aluminum (Al) is a neurotoxicant; however, efforts to understand Al toxicity are limited by the lack of a quantitative biomarker of cumulative exposure. Bone Al measurements may address this need. Here, we describe and compare non-invasive bone Al measurements with fingernail Al and Al cumulative exposure indices (CEIs). METHODS: We completed a cross-sectional study of 43 factory workers in Zunyi, China. Bone Al measurements were taken with a compact in-vivo neutron activation analysis system (IVNAA). Fingernail samples were analyzed using inductively coupled plasma mass spectrometry. CEIs, based on self-reported work history and prior literature, were calculated for the prior 5, 10, 15, 20 years and lifetime work history. Linear regressions adjusted for age and education compared fingernail Al and Al CEIs with bone Al. RESULTS: Median (interquartile range (IQR)) Al measurements were: 15 µg/g dry bone (IQR = 28) for bone Al; 34.9 µg/g (43.3) for fingernail; and 24 (20) for lifetime CEI. In adjusted regression models, an increase in 15-year CEI was significantly associated with increased bone Al (ß = 0.91, 95% confidence interval (CI): 0.16, 1.66). Associations of bone Al with 10- and 20-year CEI were approaching statistical significance (ß = 0.98, 95% CI: -0.14, 2.1; ß = 0.59, 95% CI: -0.01, 1.18, respectively). Other models were not statistically significant. CONCLUSIONS: Bone Al was significantly associated with 15-year Al CEI, but not other Al CEIs or fingernail Al. Bone Al may be a useful measure of cumulative, rather than short-term, Al exposure. Additional refinement of this method is ongoing.

Determination of bone sodium (Na) and Na exchange in pig leg using in vivo neutron activation analysis (IVNAA).

OBJECTIVE: The locations of sodium (Na) storage and its exchange mechanisms in the body are not well known. Understanding tissue Na storage and exchange is important for understanding the impact of Na intake, absorption, and retention on human health, especially on the risk of developing chronic diseases. The purpose of this study was to investigate the application of a deuterium-deuterium (DD) neutron generator-based IVNAA system in Na nutrition studies. APPROACH: The right legs of two live pigs, one on a low Na diet and one on a high Na diet, both for 14 d, were irradiated inside a customized irradiation cave for 10 min (45 mSv dose to the leg) and then measured with a 100% efficient high purity germanium detector (HPGe). The spectra were analyzed to obtain the net Na counts at different time points. Bone Na concentrations were calculated using the calibration created with Na bone phantoms. MAIN RESULTS: The results show that the difference in bone Na to calcium between the pigs on high versus low Na diets was 466 ± 137 ppm. The estimated bone Na to calcium concentrations were 1166 ± 80 and 1631 ± 111 ppm for low and high Na diet pigs, respectively. Analysis also shows rapid exchange of Na in the leg during the first 2 h measurements, while the exchange was minimal at the second and third 2 h measurements, taken 7 and 21 h post irradiation. The exchange decay time of Na in the leg was 51 min for the first measurement, and there was no significant change of Na activities between 2-21 h. SIGNIFICANCE: With these results, we conclude there is a non or low exchangeable compartment (likely to be bone) for Na storage and that DD neutron generator-based IVNAA is a useful method for determining tissue Na distribution in nutrition studies.

The association of bone, fingernail and blood manganese with cognitive and olfactory function in Chinese workers.

Occupational manganese (Mn) exposure has been associated with cognitive and olfactory dysfunction; however, few studies have incorporated cumulative biomarkers of Mn exposure such as bone Mn (BnMn). Our goal was to assess the cross-sectional association between BnMn, blood Mn (BMn), and fingernail Mn (FMn) with cognitive and olfactory function among Mn-exposed workers. A transportable in vivo neutron activation analysis (IVNAA) system was designed and utilized to assess BnMn among 60 Chinese workers. BMn and FMn were measured using inductively coupled plasma mass spectrometry. Cognitive and olfactory function was assessed using Animal and Fruit Naming tests, World Health Organization/University of California-Los Angeles Auditory Verbal Learning Test (AVLT) and the University of Pennsylvania Smell Identification Test (UPSIT). Additional data were obtained via questionnaire. Regression models adjusted for age, education, factory of employment, and smoking status (UPSIT only), were used to assess the relationship between Mn biomarkers and test scores. In adjusted models, increasing BnMn was significantly associated with decreased performance on average AVLT scores [ß (95% confidence interval (CI)) = -0.65 (-1.21, -0.09)] and Animal Naming scores [ß (95% CI) = -1.54 (-3.00, -0.07)]. Increasing FMn was significantly associated with reduced performance measured by the average AVLT [ß (95% CI) = -0.35 (-0.70, -0.006)] and the difference in AVLT scores [ß (95% CI) = -0.40 (-0.77, -0.03)]. BMn was not significantly associated with any test scores; no significant associations were observed with Fruit Naming or UPSIT tests. BnMn and FMn, but not BMn, are associated with cognitive function in Mn-exposed workers. None of the biomarkers were significantly associated with olfactory function.

Blood lead, bone lead and child attention-deficit-hyperactivity-disorder-like behavior.

BACKGROUND AND OBJECTIVE: Mounting evidence showed that lead exposure increased the risk of child attention-deficit-hyperactivity disorder (ADHD). Epidemiologic studies have typically used the blood-lead as a biomarker of lead exposure; blood-lead levels mostly reflect recent lead exposure. However, few studies have examined the relationship between bone-lead, a biomarker of cumulative exposure, and ADHD. Therefore, we aimed to compare the associations of bone-lead vs blood-lead levels with child ADHD symptoms and comorbidities. METHODS: A total of 164 children aged 3-15 years were enrolled during 2014-2015. The Vanderbilt-ADHD-Diagnostic-Parent-Rating Scale (VADPRS) was used to evaluate the children's ADHD symptoms and comorbidities. Children's blood and bone lead concentrations were assessed, the latter using a non-invasive K-X-ray-fluorescence technique. According to blood-lead levels, children were classified into high (blood-lead ≥ 10.0 µg/dL) and low (blood-lead < 10.0 µg/dL) blood-lead groups. According to bone-lead levels, children were classified into high (bone-lead ≥ 2.66 µg/g) and low (bone-lead < 2.66 µg/g) bone-lead groups. We associated blood/bone lead with VADPRS data using multi-variable binary logistic regression models. RESULTS: Children in the high blood-lead group had higher hyperactivity/impulsivity (P = 0.02) scores than the corresponding low blood-lead group. Children in the high bone-lead group had higher hyperactivity/impulsivity (P = 0.02) and oppositional-defiant-disorder (ODD) (P = 0.03) scores than the corresponding low bone-lead group. After adjusting for relevant confounders, children in the high bone-lead group were more likely to have ODD-behavior than the low group (OR = 6.7, 95%CI: 1.2-36.5). However, no adjusted association was observed between blood-lead and any ADHD-domain score. CONCLUSION: High levels of cumulative lead exposure in children may be an independent risk factor of ODD-behavior.

A Dosimetry Study of Portable X-ray Fluorescence in Vivo Metal Measurements.

Portable x-ray fluorescence devices have grown in popularity for possible metal exposure assessment using in vivo measurements of bone and toenail. These measurements are accompanied by a small radiation dose, which is typically assessed by radiation safety committees to be minimal. However, an understanding of precise dose under different instrument conditions is still needed. This study set out to do a thorough investigation of the exact dose measurements using optically stimulated dosimeters, thermoluminescent dosimeters, and simulation with a Monte Carlo N-Particle transport code to assess the skin and total-body effective dose typical of portable x-ray fluorescence devices. We showed normal linear relationships between measurement time, x-ray tube current, and radiation dose with the device, and we showed a second order polynomial relationship with increasing voltage and radiation dose. Dose was quantified using thermoluminescent dosimeters, optically stimulated dosimeters, and simulations, which gave similar dose estimations. Skin dose for a standard 50-kV, 40-µA measurement for bone and toenail in vivo was 48.5 and 28.7 mSv, respectively, according to simulation results. Total-body effective dose was shown as 3.4 and 2.0 µSv for in vivo bone and toenail measurements, respectively, for adults using the portable x-ray fluorescence device.

Childhood lead biokinetics and associations with age among a group of lead-poisoned children in China.

Childhood lead exposure has been shown to have a significant effect on neurodevelopment. Many of the biokinetics involved with lead biomarkers in children still remain unknown. Two hundred fifty (157 in the exposed group and 93 controls) children were enrolled in our study and lead exposed children returned for multiple visits for measurement of blood and bone lead and chelation treatment. We demonstrated that the correlation between blood and bone lead increased with subsequent visits. We calculated the blood lead half-life for 50 patients, and found a significant (p-value < 0.001) positive correlation with age. For ages 1-3 years (N = 17), the blood lead half-life was found to be 6.9 ± 4.0 days and for 3+ years it was found to be (N = 33) 19.3 ± 14.1 days. In conclusion, the turnover of lead in children is faster than in adults. Our results indicate that blood lead is a more acute biomarker of exposure than previously thought, which will impact studies of children's health using blood lead as a biomarker.

Validation of x-ray fluorescence measurements of metals in toenail clippings against inductively coupled plasma mass spectrometry in a Nigerian population.

OBJECTIVE: Metal exposures have been linked with many adverse health outcomes affecting nearly every system in the body. Exposure to metals has been tracked primarily using blood. Blood metal concentrations have drawbacks as biomarkers stemming from the metals' short biologic half-lives, shipping and storage requirements, and invasive collection procedures. Toenails, which capture a longer exposure period, can be collected non-invasively and stored at room temperature, and can be more feasible and cost-effective for large-scale population studies. APPROACH: Inductively coupled plasma mass spectrometry (ICP-MS) has been used for analysis of toenail metal concentrations, but x-ray fluorescence (XRF) has many advantages in versatility and cost effectiveness over these analyses. This study compared toenail concentrations of manganese (Mn) and lead (Pb) measured with XRF against ICP-MS, in samples collected from 20 adults in Nigeria. To do this we developed a novel calibration method that corrects XRF measurements for toenail weight and thickness to reduce the variability in XRF measurements of toenail clippings. MAIN RESULTS: We found a high correlation (R = 0.91) between toenail manganese metal measurements made with XRF and ICP-MS and a correlation of (R = 0.32) between toenail lead XRF and ICP-MS with over half of the lead results below the detection limit of the instrumentation. SIGNIFICANCE: XRF can be used effectively to quantify metals at the part per million level or lower depending on the XRF equipment used in the measurements.

Development of a Cumulative Exposure Index (CEI) for Manganese and Comparison with Bone Manganese and Other Biomarkers of Manganese Exposure.

Manganese (Mn) exposure can result in parkinsonism. However, understanding of manganese neurotoxicity has been limited by the lack of a cumulative Mn biomarker. Therefore, the current goal was to develop Mn cumulative exposure indices (MnCEI), an established method to estimate cumulative exposure, and determine associations of MnCEI with blood Mn (BMn), fingernail Mn (FMn), and bone Mn (BnMn). We completed a cross-sectional study of 60 male Chinese workers. Self-reported occupational history was used to create two MnCEIs reflecting the previous 16 years (MnCEI16) and total work history (MnCEITOT). An in vivo neutron activation analysis system was used to quantify BnMn. BMn and FMn were measured using ICP-MS. Mean (standard deviation) MnCEITOT and MnCEI16 were 37.5 (22.0) and 25.0 (11.3), respectively. Median (interquartile range) BMn, FMn, and BnMn were 14.1 (4.0) μg/L, 13.5 (58.5) μg/g, and 2.6 (7.2) μg/g dry bone, respectively. MnCEI16 was significantly correlated with FMn (Spearman’s ρ = 0.44; p = 0.02), BnMn (ρ = 0.44; p < 0.01), and MnCEITOT (ρ = 0.44; p < 0.01). In adjusted regression models, MnCEI16 was significantly associated with BnMn (β = 0.03; 95% confidence interval = 0.001, 0.05); no other biomarkers were associated with MnCEI. This suggests BnMn may be a useful biomarker of the previous 16 years of Mn exposure, but larger studies are recommended.

Compact DD generator-based in vivo neutron activation analysis (IVNAA) system to determine sodium concentrations in human bone.

OBJECTIVE: This study presents the development of a noninvasive method for monitoring Na in human bone. Many diseases, such as hypertension and osteoporosis, are closely associated with sodium (Na) retention in the human body. Na retention is generally evaluated by calculating the difference between dietary intake and excretion. There is currently no method to directly quantify Na retained in the body. Bone is a storage for many elements, including Na, which renders bone Na an ideal biomarker to study Na metabolism and retention. APPROACH: A customized compact deuterium-deuterium (DD) neutron generator was used to produce neutrons for in vivo neutron activation analysis (IVNAA), with a moderator/reflector/shielding assembly optimized for human hand irradiation in order to maximize the thermal neutron flux inside the irradiation cave and to limit radiation exposure to the hand and the whole body. MAIN RESULTS: The experimental results show that the system is able to detect sodium levels in the bone as low as 16 µg Na g-1 dry bone with an effective dose to the body of about 27 µSv. The simulation results agree with the numbers estimated from the experiment. SIGNIFICANCE: This is expected to be a feasible method for measuring the change of Na in bone. The low detection limit indicates this will be a useful system to study the association between Na retention and related diseases.

Monte Carlo simulations of elemental imaging using the neutron-associated particle technique.

PURPOSE: The purpose of this study is to develop and employ a Monte Carlo (MC) simulation model of associated particle neutron elemental imaging (APNEI) in order to determine the three-dimensional (3D) imaging resolution of such a system by examining relevant physical and technological parameters and to thereby begin to explore the range of clinical applicability of APNEI to fields such as medical diagnostics, intervention, and etiological research. METHODS: The presented APNEI model was defined in MCNP by a Gaussian-distributed and isotropic surface source emitting deuterium + deuterium (DD) neutrons, iron as the target element, nine iron-containing voxels (1 cm3 volume each) arranged in a 3-by-3 array as the interrogated volume of interest, and finally, by high-purity germanium (HPGe) gamma-ray detectors anterior and posterior to the 9-voxel array. The MCNP f8 pulse height tally was employed in conjunction with the PTRAC particle tracking function to not only determine the signal acquired from iron inelastic scatter gamma-rays but also to quantitate each of the nine target voxels' contribution to the overall iron signal - each detected iron inelastic scatter gamma-ray being traced to the source neutron which incited its emission. RESULTS: With the spatial, vector, and timing information of the series of events for each relevant neutron history as collected by PTRAC, realistic grayscale images of the distribution of iron concentration in the 9-voxel array were simulated in both the projective and depth dimensions. With an overall 225 ps timing resolution, 6.25 mm2 imaging plate pixels assumed to have well localized scintillation, and a DD neutron, Gaussian-distributed source spot with a diameter of 2 mm, projective and depth resolutions of < 1 cm and <3 cm are achievable, respectively, for iron-containing voxels on the order of 1,000 ppm Fe. CONCLUSIONS: The imaging resolution offered by APNEI of target elements such as iron lends itself to potential applications in disease diagnosis and treatment planning (high resolution) as well as to ordnance and contraband detection (low resolution). However, experimental study beyond simulation is required to optimize the layout and electronic configuration of APNEI system components - including realistic shielding and phantom materials - for background signal reduction in order to accurately determine the detection limits and spatial resolution of iron and other elements of interest on a case-by-case basis.