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Introduction: Pb in bone may serve as a biomarker for cumulative Pb dose over decades. We hypothesized that adult female bone Pb concentrations (BoPb) would be significantly associated with average childhood blood Pb levels (BlPb) in a birth cohort exposed to relatively high levels of Pb from Pb paint residues., Methods: 94 African American women with a mean age of 32.7 years were recruited from the Cincinnati Lead Study (CLS) cohort. Subjects were born to women residing where there had been a high incidence of childhood Pb poisoning. Biomarkers of Pb exposure were serial BlPb concentrations spanning the prenatal period to approximately 6.5 years of age. BoPb was assessed in the tibia using the McMaster 109 Cd K-XRF fourth generation system. Covariates included nutritional variables related to bone health., Results: BlPb concentrations began to rise around 6 months of age and declined at later ages. Study participants were obese with a mean Body Mass Index of 34.4 and suboptimal vitamin D status as indicated by a mean 25-OH-D of 18.5 ng/ml. Average tibia Pb was -2.0 ± 8.6 μgPb/g bone mineral. In multiple linear regression, there was no significant association between BoPb at approximately age 30 and childhood cumulative BlPb(CumBlPb)., Discussion: Collectively, BoPb of this group of subjects was not detectable. We suggest that the reason these subjects' BoPb did not reflect their early exposure was that a significantly smaller proportion of Pb body burden resides in bone in young children. As the child grows what Pb there was in bone is diluted and any remaining signal is weak. It has been claimed that BoPb in older children, adolescents, and adults can recapitulate historical exposure to Pb during earlier development; however, in some populations, BoPb at later ages may not be an adequate biomarker to capture childhood exposure to Pb., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Iron is an essential element vital for growth and development. The severe effects on the body due to iron deficiency or overload have prompted sustained research into accurate in vivo iron measurement techniques for the past several decades. X-ray fluorescence (XRF) analysis of iron in the body has been investigated in this work because of the non-invasive nature of the technique. A system has been designed using a silicon drift detector to measure the low-energy iron K α x-rays excited in the samples by the silver x-rays from 109 Cd of energy 22 keV and 25 keV. The source is contained within a tantalum shielding cap designed to reduce the spectral background. The system was calibrated against 3D printed polylactic acid (PLA) phantoms filled with solutions of iron at various concentrations. The iron x-ray signals were normalized to a nickel x-ray signal which improved the system's reproducibility. The 3D phantoms and normalisation resulted in a linear calibration line (p < 0.001 and r 2  > 0.999). For a real-time measurement of 1800 s, the minimum detectable limit for the system was measured to be 1.35 ± 0.35 ppm which is achieved with a low radiation dose of 1.1 mSv to the skin surface. This low detection limit and low dose mean the system is feasible for application to human measurements in both iron deficiency and overload disease. The system will proceed to post-mortem validation studies prior to in vivo system efficacy testing., (Creative Commons Attribution license.)

A small pilot study was conducted to test whether the technique of in vivo neutron activation analysis could measure bone aluminum levels in 15 miners who had been exposed to McIntyre Powder over 40 years prior. All miners were over 60 years of age, had worked in mines that used McIntyre Powder, and were sufficiently healthy to travel from northern to southern Ontario for the measurements. Individual aluminum levels were found to be significantly greater than zero with 95% confidence ( p  < 0.05) in 7 out of the 15 miners. The inverse variance weighted mean of the 15 participants was 21.77 ± 2.27µgAl/gCa. This was significantly higher ( p  < 0.001) than in a group of 15 non-occupationally exposed subjects of a comparable age from Southern Ontario who had been measured in a previous study. The inverse variance weighted mean bone aluminum content in the non-occupationally exposed group was 3.51 ± 0.85µgAl/gCa. Since the use of McIntyre Powder ceased in 1979, these subjects had not been exposed for more than 40 years. Calculations of potential levels at the cessation of exposure in the 1970s, using a biological half-life of aluminum in bone of 10 to 20 years predicted levels of bone aluminum comparable with studies performed in dialysis patients in the 1970s and 1980s. This pilot study has shown that the neutron activation analysis technique can determine differences in bone aluminum between McIntyre Powder exposed and non-exposed populations even though 40 years have passed since exposure ceased. The technique has potential application as a biomarker of exposure in cross-sectional studies of the health consequences of exposure to McIntyre Powder.

Biophoton emission leading to bystander effects (BEs) was shown in beta-irradiated cells; however, technical challenges precluded the analysis of the biophoton role in gamma-induced BEs. The present work was to design an experimental approach to determine if, what type, and how many biophotons could be produced in gamma-irradiated cells. Photon emission was measured in HCT116 p53 +/+ cells irradiated with a total dose of 22 mGy from a cesium-137 source at a dose rate of 45 mGy/min. A single-photon detection unit was used and shielded with lead to reduce counts from stray gammas reaching the detector. Higher quantities of photon emissions were observed when the cells in a tissue culture vessel were present and being irradiated compared to a cell-free vessel. Photon emissions were captured at either 340 nm (in the ultraviolet A [UVA] range) or 610 nm. At the same cell density, radiation exposure time, and radiation dose, HCT116 p53 +/+ cells emitted 2.5 times more UVA biophotons than 610-nm biophotons. For the first time, gamma radiation was shown to induce biophoton emissions from biological cells. As cellular emissions of UVA biophotons following beta radiation lead to BEs, the involvement of cellular emissions of the same type of UVA biophotons in gamma radiation-induced BEs is highly likely., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Today, patients undergoing dialysis are at low risk for aluminum-induced dementia. Workers are unlikely to experience cadmium-induced emphysema and the public's exposure to lead is an order of magnitude lower than in 1970. The research field of in vivo elemental analysis has played a role in these occupational and environmental health improvements by allowing the effects of people's chronic exposure to elements to be studied using non-invasive, painless, and relatively low-cost technology. From the early 1960s to the present day, researchers have developed radiation-based systems to measure the elemental content of organs at risk or storage organs. This reduces the need for (sometimes painful) biopsy and the risk of infection. Research and development has been undertaken on forty-nine in vivo measurement system designs. Twenty-nine different in vivo elemental analysis systems, measuring 22 different elements, have been successfully taken from design and testing through to human measurement. The majority of these systems employ either neutron activation analysis or x-ray fluorescence analysis as the basis of the measurement. In this review, we discuss eight of the successful systems, explaining the rationale behind their development, the methodology, the health data that has resulted from application of these tools, and provide our opinion on potential future technical developments of these systems. We close by discussing four technologies that may lead to new directions and advances in the whole field.

Objective: To report additional gadolinium bone and urine data that can contribute to gaps in knowledge with respect to gadolinium uptake and retention in the body., Approach: In vivo measurements of gadolinium retention in the tibia bone were performed on individuals self-identified as exhibiting symptoms of gadolinium toxicity as a result of receiving GBCA, as well as on control individuals. Gadolinium urine measurements for controls, symptomatic exposed, and non-symptomatic exposed were conducted through Mayo Medical Laboratories., Main Results: Gadolinium bone concentration in the exposed group is significantly higher than the control group (p < 0.01), with a significant difference between symptomatic and non-symptomatic (p < 0.01), using a one-tailed t test on variance-weighted means. Gadolinium urine levels in both control subjects and non-symptomatic exposed subjects are significantly lower than symptomatic exposed subjects (p ≤ 0.05). A linear regression analysis for gadolinium urine levels and GBCA dose resulted in a positive linear relationship (R 2 = 0.91, p < 0.01). Gadolinium levels in urine and gadolinium concentration in bone were found to have a non-significant relationship (R 2 = 0.11, p = 0.3)., Significance: Significant differences in gadolinium levels in bone and urine are observed between individuals experiencing symptoms of gadolinium toxicity and for those who are not exhibiting symptoms. No correlation was observed between gadolinium in bone and gadolinium excreted in urine, suggesting that the retention of gadolinium in the body is complicated, involving multiple long-term storage sites.

Purpose To perform a preliminary evaluation of a noninvasive measurement system to assess gadolinium deposition in bone and to investigate the relationship between the administration of gadolinium-based contrast agents (GBCAs) and gadolinium retention in bone. Materials and Methods In vivo measurement of gadolinium retention in tibia bones was performed in 11 exposed subjects who previously received GBCAs (six exposed subjects were from a study performed 5 years previously involving injection of GBCAs in healthy volunteers; five exposed subjects had self-reported GBCA exposure), and 11 sex- and age-matched control subjects without a history of GBCA exposure. Each subject underwent one measurement of gadolinium retention in the tibia with x-ray fluorescence in a laboratory at McMaster University. A one-tailed t test was performed to compare gadolinium concentration in the exposed group with that in the control group. The relationship between the dose of GBCA administered and the gadolinium concentration measured in bone was analyzed with linear regression. Results Gadolinium concentration in bone was significantly higher in exposed subjects (mean, 1.19 μg Gd/g bone mineral ± 0.73 [standard deviation]) than in control subjects (mean, -1.06 μg Gd/g bone mineral ± 0.71) (P = .01). There was also a positive correlation between the dose of GBCA administered and the gadolinium concentration measured in bone (R 2 = 0.41); gadolinium concentration in bone increased by 0.39 μg Gd/g bone mineral ± 0.14 per 1 mL of GBCA administered. Gadolinium was detected in bone up to 5 years after one GBCA administration. Conclusion This x-ray fluorescence system is capable of measuring gadolinium deposition in bone noninvasively in vivo. Gadolinium can be retained in bone after one dose of GBCA in healthy subjects. © RSNA, 2017 Online supplemental material is available for this article.

Objective and Approach: A study, conducted in Toronto, Canada, between 2009 and 2011, measured the bone lead concentrations of volunteers aged 1-82 years using in vivo x-ray fluorescence (XRF) technology., Main Results: Bone lead levels were lower compared to Ontario in vivo XRF studies from the early 1990s. In adults, the slope of tibia lead content versus age was reduced by 36-56%, i.e. bone lead levels for a given age group were approximately half compared to the same age group 17 years prior. Further, bone lead levels of individuals fell over that time period. In 2010, an average person aged 57 years had a bone lead level approximately 1/3 less than their bone lead level age 40 years in 1993. Using this data, the half-lives of lead in the tibia were estimated as 7-26 years. Tibia lead levels were found to be low in children. The reduction in bone tibia content in children was not significant (p  =  0.07), but using data from additional north eastern US studies, there is evidence that childhood tibia stores are lower than in the 1990s., Significance: In vivo XRF analysis shows that there has been a reduction in the level of lead in bone in Canada over the last two decades. Public health measures have been very successful in reducing ongoing exposure to lead and in reducing bone lead stores.

Objective: Recent evidence of gadolinium (Gd) deposition in bones of healthy individuals who have previously received Gd-based contrast agents (GBCAs) for MRI has led to a demand for in vivo measurement techniques. The technique of x-ray fluorescence provides a low risk and painless method to assess Gd deposition in bone, and has the potential to be a useful clinical tool. However, interpatient variability creates a challenge while performing in vivo measurements., Approach: We explored the use of coherent normalization, which involves normalizing the Gd K x-rays to the coherent scattered γ-ray from the excitation source, for bone Gd measurements through a series of phantom-based experiments and Monte Carlo simulations., Main Results: We found coherent normalization is able to correct for variation in overlying tissue thickness over a wide range (0-12.2 mm). The Gd signal to coherent signal ratio is independent of tissue thickness for both experiments and Monte Carlo simulations., Significance: Coherent normalization has been demonstrated to be used in practice with normal healthy adults to improve in vivo bone Gd measurements.

The Figure-Of-Merit (FOM) performance, a combination of detection limit and dose, is compared between two generations of handheld X-Ray Fluorescence (XRF) spectrometers for the feasibility of in vivo XRF measurement of arsenic (As) in skin. The Olympus InnovX Delta model analyzer (40 kVp using either 37 or 17μA) was found to show improvements in Minimum Detection Limit (MDL) using arsenic As-doped skin calibration phantoms with bulk tissue backing, when compared to the first generation InnovX Alpha model (40kVp, 20μA) in 120s measurements. Differences between two different definitions of MDL are discussed. On the Delta system, an MDL of (0.462±0.002) μg/g As was found in phantoms, with a nylon backing behind to mimic bulk tissue behind skin. The equivalent and effective doses were found to be (10±2) mSv and ~7×10 -3 μSv respectively for the Alpha and (15±4) mSv and ~8×10 -3 μSv respectively for the Delta system in 120s exposures. Combining MDL and effective dose, a lower (better) FOM was found for the Delta, (1.7±0.4) ppm mSv 1/2 , compared to (4.4±0.5) ppm mSv 1/2 for the Alpha model system. The Delta analyzer demonstrates improved overall system performance for a rapid 2-min measurement in As skin phantoms, such that it can be considered for use in populations exposed to arsenic., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To study the age and sex influence on bone and blood lead concentrations in a cohort of the general population living in Toronto., Approach: A 109 Cd K x-ray fluorescence (KXRF) measurement system was used from 2009 to 2011 in a study that measured the bone lead (Pb) concentration of 263 environmentally exposed individuals residing in Toronto, Ontario, Canada. Tibia (cortical bone) and calcaneus (trabecular bone) lead contents were measured in 134 males and 129 females between 1 and 82 years of age. Whole blood Pb concentration was measured by TIMS (thermal ionization mass spectrometer). Tibia (Ti) and calcaneus (Cal) Pb were examined versus the age of participants, taking into account uncertainties in bone Pb measurement values., Main Results: No significant sex differences were observed in any of the age categories. Participants older than 50 years of age demonstrated the highest concentrations of Pb in their blood, tibia, and calcaneus bones., Significance: In most of the previous publications, uncertainty was not considered in the regression model of bone Pb and age. However, in this paper, we adjusted the bone Pb values for the uncertainty level. This had a significant influence in regression models of bone Pb and thus we recommend that uncertainty be considered in future studies.

The safety of using Gd in MRI contrast agents has recently been questioned, due to recent evidence of the retention of Gd in individuals with healthy renal function. Bone has proven to be a storage site for Gd, as unusually high concentrations have been measured in femoral heads of patients undergoing hip replacement surgery, as well as in autopsy samples. All previous measurements of Gd in bone have been invasive and required the bone to be removed from the body. X-ray fluorescence (XRF) offers a non-invasive and non-destructive method for carrying out in vivo measurements of Gd in humans. An updated XRF system provides improved detection limits in a short measurement time of 30-min. A new four-detector system and higher activity Cd-109 excitation source of 5GBq results in minimum detection limits (MDLs) of 1.64-1.72μgGd/g plaster for an average overlaying tissue thickness of the tibia. These levels are well within the range of previous in vitro Gd measurements. Additional validation through comparison with ICP-MS measurements has confirmed the ability of the XRF system for detecting Gd further, proving it is a feasible system to carry out human measurements., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The time-dependent behaviour of sodium and chlorine was studied as a spinoff from a study of aluminum in the hand of subjects suffering from Alzheimer's disease and a control group, involving 15 Alzheimer's and 16 control subjects with an age range of 63-89 years. This was achieved using the in vivo neutron activation analysis system developed at McMaster University for the non-invasive measurement of aluminum, where a subject's hand is placed in a beam of accelerator-based thermalized neutrons, which activates elements by neutron capture. Following irradiation, the subject's hand is placed in a detection system comprising 9 NaI(Tl) detectors arranged in a 4π geometry to measure activated elements. The redistribution half-lives of the activation products 24 Na and 38 Cl from the hand were determined after correction for the physical half-life, by means of sequential analysis of the residual activity in the hand. The kinetic behaviours of sodium and chlorine were best characterized by an exponential function corresponding to the rapidly exchangeable pool. The mean redistribution half-lives from the hand for sodium and chlorine in the control subjects were 40.5  ±  17.4 min and 24.2  ±  8.5 min, respectively. For Alzheimer's disease subjects the mean redistribution half-lives were 58.2  ±  36.1 min for sodium and 33.6  ±  16.7 min for chlorine. There was no significant difference in chlorine and sodium redistribution half-lives between the Alzheimer's disease and control group subjects. These results are promising, given that the irradiation and counting protocol were optimized for the aluminum study, rendering them suboptimal for analyzing other elements and their rate of change with time. Further improvements include optimizing the irradiation protocol, longer counting times, and measuring the activity in the un-irradiated hand in various time intervals following irradiation.

An existing system at McMaster University has been used for the in vivo measurement of aluminum in human bone. Precise and detailed analysis approaches are necessary to determine the aluminum concentration because of the low levels of aluminum found in the bone and the challenges associated with its detection. Phantoms resembling the composition of the human hand with varying concentrations of aluminum were made for testing the system prior to the application to human studies. A spectral decomposition model and a photopeak fitting model involving the inverse-variance weighted mean and a time-dependent analysis were explored to analyze the results and determine the model with the best performance and lowest minimum detection limit. The results showed that the spectral decomposition and the photopeak fitting model with the inverse-variance weighted mean both provided better results compared to the other methods tested. The spectral decomposition method resulted in a marginally lower detection limit (5μg Al/g Ca) compared to the inverse-variance weighted mean (5.2μg Al/g Ca), rendering both equally applicable to human measurements., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Aluminum, being the most abundant metal in the earth's crust, is widely distributed in the environment, and is routinely taken up by the human body through ingestion and inhalation. Aluminum is not considered an essential element and it can be toxic in high concentrations. Most of the body burden of aluminum is stored in the bones. Aluminum has been postulated to be involved in the causality of Alzheimer's disease. A system for non-invasive measurement of bone aluminum using the in vivo neutron activation analysis technique has been developed and previously reported in the literature by our group. The results are reported as ratio of Al to Ca in order to eliminate the variations in beam parameters and geometry as well as the physical variations among the subjects such as size of the hand and bone structure. This pilot study included 30 subjects, 15 diagnosed with Alzheimer's disease in mild and moderate stages and 15 control subjects, all of whom were 60 years of age or older. The mean value of aluminum for the control group was 2.7±8.2μg Al/g Ca (inverse-variance weighted mean 3.5±0.9μg Al/g Ca) and for the Alzheimer's disease subjects was 12.5±13.1μg Al/g Ca (inverse-variance weighted mean 7.6±0.6μg Al/g Ca). The difference between the mean of the Alzheimer's disease group and the mean of the control group was 9.8±15.9μg Al/g Ca, with a p-value of 0.02. An age-dependent linear increase in bone aluminum concentration was observed for all subjects. The difference in serum aluminum levels between the two groups did not reach significance.

Gadolinium (Gd) based contrast agents have been commonly used over the past three decades to improve contrast in magnetic resonance imaging. These complexes, originally thought to be stable and clear from the body shortly after administration, have been shown to dissociate to a small extent and deposit in organs such as bone. A safe and non-invasive method for measuring Gd in bone is necessary for further exploring Gd retention in the body following the administration of a contrast agent. A feasibility study using a K x-ray fluorescence (K-XRF) system to measure Gd in human tibias was investigated. Bone phantoms mimicking human tibia were created with Gd concentrations ranging from 0 to 120ppm. The minimum detection limit (MDL) was calculated from 20-hour and 7-hour phantom measurements with a source activity of 0.11GBq. All MDL values were scaled to a more realistic measurement time of 30-minutes with a stronger source. Scaling arguments were based on activity ratio, measurement time, and system dead time. The MDL for a 1GBq source was estimated to be 3.60-3.64ppm, for an average range of tissue thicknesses overlaying a human tibia. For a stronger source of 5GBq and a four detector cloverleaf system, the MDL was estimated to be 1.49-1.52ppm. Determined and predicted MDLs are within the range of previous in-vitro Gd measurement data. The K-XRF system shows promising results for detecting Gd in bone and should be seriously considered for in-vivo measurements., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The goals of the present study were to develop a (170)Tm radioisotope and generate a K XRF spectrum of mercury. Thulium foil and thulium oxide powder were both tested for impurities and the latter was found to be a better prospect for further studies. The (170)Tm radioisotope was developed from thulium oxide powder following the method of disolution and absorption. A suitable source holder and collimator were also designed based on Monte Carlo simulations. Using the radioisotope thus developed, a mercury XRF spectrum was successfully generated., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

An in-house custom I-125 excited in vivo x-ray fluorescence (IVXRF) system was used to perform bone strontium (Sr) measurements in individuals suffering from osteoporosis and/or osteopenia. These individuals, who were self-administering with Sr supplements of their choice, were measured frequently, ranging from weekly to biweekly to monthly, over four years, as part of the Ryerson and McMaster Sr in Bone Research Study. Based on these data collected, data from eight subjects were used to perform kinetic modeling of Sr in human bone. Power and exponential models were used to model the data based on one and two compartmental systems. Model parameters included: mean normalized baseline bone Sr signal, half-life and bone Sr uptake. A one compartmental exponential model applied to finger and ankle bone measurements gave half-lives of (508  ±  331) d and (232  ±  183) d, respectively, but did not show statistically significant differences (p  =  0.087 96). However, the values fall within literature estimates. When a two compartmental model was applied to finger bone measurements, half-lives of (300  ±  163) d and (2201  ±  1662) d were observed. Ankle bone data gave half-lives of (156  ±  117) d and (1681  ±  744) d. A two sample t-test, assuming unequal variances, showed these half-lives to be statistically different in both the finger and ankle bone measurements (p  =  0.0147 and p  =  0.00711, respectively). Common kinetic parameters amongst the different subjects could not be unambiguously identified due to the wide scatter of data, leading to an inconclusive kinetic model. The wide distribution of data is suggested to be physiological since technical and positioning factors were eliminated as possible causes. This outcome indicates the need for a more controlled study and further understanding of the physiological mechanism of Sr absorption.

Aluminum, as an abundant metal, has gained widespread use in human life, entering the body predominantly as an additive to various foods and drinking water. Other major sources of exposure to aluminum include medical, cosmetic, and occupational routes. As a common environmental toxin, with well-known roles in several medical conditions such as dialysis encephalopathy, aluminum is considered a potential candidate in the causality of Alzheimer's disease. Aluminum mostly accumulates in the bone, which makes bone an indicator of the body burden of aluminum and an ideal organ as a proxy for the brain. Most of the techniques developed for measuring aluminum include bone biopsy, which requires invasive measures, causing inconvenience for the patients. There has been a considerable effort in developing non-invasive approaches, which allow for monitoring aluminum levels for medical and occupational purposes in larger populations. In vivo neutron activation analysis, a method based on nuclear activation of isotopes of elements in the body and their subsequent detection, has proven to be an invaluable tool for this purpose. There are definite challenges in developing in vivo non-invasive techniques capable of detecting low levels of aluminum in healthy individuals and aluminum-exposed populations. The following review examines the method of in vivo neutron activation analysis in the context of aluminum measurement in humans focusing on different neutron sources, interference from other activation products, and the improvements made in minimum detectable limits and patient dose over the past few decades.

In recent years, in vivo measurement systems of arsenic in skin by K-shell x-ray fluorescence (XRF) have been developed, including one which was applied in a pilot study of human subjects. Improved tube-based approaches suggest the method can be further exploited for in vivo studies. Recently, it has been suggested that selenium deficiency is correlated with arsenic toxicity. A non-invasive measurement of both elements could therefore be of potential interest. The main aim of this current study was to evaluate and compare the performance of an upgraded portable XRF system and an advanced version of the benchtop XRF system for both selenium and arsenic. This evaluation was performed in terms of arsenic and selenium Kα detection limits for a 4W gold anode Olympus InnovX Delta portable analyzer (40 kVp) in polyester resin skin-mimicking phantoms. Unlike the polychromatic source earlier reported in the literature, the benchtop tube-based technique involves monochromatic excitation (25 W silver anode, manufactured by x-ray optics, XOS) and a higher throughput detector type. Use of a single exciting energy allows for a lower in vivo dose delivered and superior signal-noise ratio. For the portable XRF method, arsenic and selenium minimum detection limits (MDLs) of 0.59  ±  0.03 ppm and 0.75  ±  0.02 ppm respectively were found for 1 min measurement times. The MDLs for arsenic and selenium using the benchtop system were found to be 0.35  ±  0.01 ppm and 0.670  ±  0.004 ppm respectively for 30 min measurement times. In terms of a figure of merit (FOM), allowing for dose as well as MDL, the benchtop system was found to be superior for arsenic and the two systems were equivalent, within error, for selenium. We shall discuss the performance and possible improvements of each system, their ease of use and potential for field application.

The Canadian population is currently subject to low, chronic lead exposure and an understanding of its effects is of great significance to the population's health. Such low exposure is difficult to measure directly; approximation by physiologically based modeling may provide a preferable approach to population analysis. The O'Flaherty model of lead kinetics is based on an age-dependent approach to human growth and development and devotes special attention to bone turnover rates. Because lead is a bone-seeking element, the model was deemed ideal for such an analysis. Sample from 263 individuals of various ages from the Greater Toronto Area were selected to evaluate the applicability of the current version of the O'Flaherty model to populations with low lead exposure. For each individual, the input value of lead exposure was calibrated to match the output value of cortical bone lead to the individual's measured tibia lead concentration; the outputs for trabecular bone, blood, and plasma lead concentrations obtained from these calibrations were then compared with the subjects' measured calcaneus, blood, and serum lead concentrations, respectively. This indicated a need for revision of the model parameters; those for lead binding in blood and lead clearance from blood to bone were adjusted and new outputs were obtained in the same fashion as before. Model predictions of trabecular lead concentration did not agree with measurements in the calcaneus. The outputs for blood and plasma lead concentrations were highly scattered and, on an individual level, inconsistent with corresponding measurements; however, the general trends of the outputs matched those of the measurements reasonably well, which indicates that the revised blood lead binding and lead clearance parameters may be useful in future studies. Overall, the analysis showed that with the revisions to the model discussed here, the model should be a useful tool in the analysis of human lead kinetics and body burden in populations characterized by low, chronic exposure to lead from the general environment.

Hand bone equivalent phantoms (250 ml) carrying selenium in various amounts were irradiated and counted for in vivo neutron activation analysis (IVNAA) by employing a 4π NaI(TI) based detection system. During the analysis of counting data, a feature at a higher energy than the gamma ray peak from (77m)Se (0.162 MeV) was observed at 0.197 MeV. Further investigations were made by preparing water phantoms containing only de-ionized water in 250 ml and 1034 ml quantities. Neutrons were produced by the (7)Li(p,n)(7)Be reaction using the high beam current Tandetron accelerator. Phantoms were irradiated at a fixed proton energy of 2.3 MeV and proton currents of 400 μA and 550 μA for 30 s and 22 s respectively. The counting data saved using the 4π NaI(TI) detection system for 10 s intervals in anticoincidence, coincidence and singles modes of detection were analyzed. Areas under gamma peaks at energies 0.197 MeV and 1.357 MeV were computed and half-lives from the number of counts for the two peaks were established. It was concluded that during neutron activation of water phantoms, oxygen-18 is activated, producing short-lived radioactive 19O having T(1/2)  =  26.9 s. Induced activity from 19O may contribute spectral interference in the gamma ray spectrum. This effect may need to be taken into account by researchers while carrying out IVNAA of biological subjects.

Selenium (Se) is an element that, in trace quantities, plays an important role in the normal function of a number of biological processes in humans. Many studies have demonstrated that selenium deficiency in the body may contribute to an increased risk for certain neoplastic, cardiovascular, osseous, and nervous system diseases including retardation of bone formation. However, at higher concentrations Se is cytotoxic. For these reasons it is desirable to have a means of monitoring selenium concentration in humans.This paper presents the outcome of a feasibility study carried out for measuring selenium in humans using in vivo neutron activation analysis (IVNAA). In this technique a small dose of neutrons is delivered to the organ of interest, the neutrons are readily captured by the target nuclei, and the γ-rays given off are detected outside of the body. For the present study, human hand (bone) tissue equivalent phantoms were prepared with varying amounts of Se. These were irradiated by a low energy fast neutron beam produced by the (7)Li(p,n)(7)Be reaction employing the high beam current Tandetron accelerator. The counting data saved using a 4π NaI(TI) detection system were analyzed. The selenium was detected via the neutron capture reaction, (76)Se(n,γ)(77 m)Se, whereas calcium was detected through the (48)Ca(n,γ)(49)Ca reaction for the purpose of normalization of the Se signals to the calcium signals. From the calibration lines drawn between Se/Ca concentrations and Se/Ca counts ratio, the minimum detection limits (MDLs) were computed for two sets of phantoms irradiated under different irradiation parameters.In this study the optimized MDL value was determined to be 81 ng g(-1) (Se/phantom mass) for an equivalent dose of 188 mSv to the phantom. This MDL was found at least 10 times lower than the reported data on Se concentration measured in bone tissues. It was concluded that the NAA technique would be a feasible means of performing in vivo measurements of selenium in humans. Currently the data on in vivo measurement of selenium in humans are limited; the results of the present study would greatly contribute to the present data.

Conflicting evidence suggests that bone lead or blood lead may reduce areal bone mineral density (BMD). Little is known about how lead at either compartment affects bone structure. This study examined postmenopausal women (N=38, mean age 76 ± 8, body mass index (BMI): 26.74 ± 4.26 kg/m(2)) within the Hamilton cohort of the Canadian Multicentre Osteoporosis Study (CaMos), measuring bone lead at 66% of the non-dominant leg and at the calcaneus using (109)Cadmium X-ray fluorescence. Volumetric BMD and structural parameters were obtained from peripheral quantitative computed tomography images (200 μm in-plane resolution, 2.3 ± 0.5mm slice thickness) of the same 66% site and of the distal 4% site of the tibia length. Blood lead was measured using atomic absorption spectrometry and blood-to-bone lead partition coefficients (PBB, log ratio) were computed. Multivariable linear regression examined each of bone lead at the 66% tibia, calcaneus, blood lead and PBB as related to each of volumetric BMD and structural parameters, adjusting for age and BMI, diabetes or antiresorptive therapy. Regression coefficients were reported along with 95% confidence intervals. Higher amounts of bone lead at the tibia were associated with thinner distal tibia cortices (-0.972 (-1.882, -0.061) per 100 μg Pb/g of bone mineral) and integral volumetric BMD (-3.05 (-6.05, -0.05) per μg Pb/g of bone mineral). A higher PBB was associated with larger trabecular separation (0.115 (0.053, 0.178)), lower trabecular volumetric BMD (-26.83 (-50.37, -3.29)) and trabecular number (-0.08 (-0.14, -0.02)), per 100 μg Pb/g of bone mineral after adjusting for age and BMI, and remained significant while accounting for diabetes or use of antiresorptives. Total lead exposure activities related to bone lead at the calcaneus (8.29 (0.11, 16.48)) and remained significant after age and antiresorptives-adjustment. Lead accumulated in bone can have a mild insult on bone structure; but greater partitioning of lead in blood versus bone revealed more dramatic effects on both microstructure and volumetric BMD., Competing Interests: Andy Kin On Wong, Karen A. Beattie, Aakash Bhargava, Marco Cheung, Colin E. Webber, David Chettle, Alexandra Papaioannou, and Jonathan D. Adachi declare that they have no conflicts of interest., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Non-invasive in vivo neutron activation analysis (NAA) was used to measure the fluorine concentration in 35 people in Hamilton, Ontario, Canada. Measurement and precision data of this second generation NAA system were determined in 2013, and the results were compared with the performance of a first generation system used in a pilot study of 33 participants from the Hamilton area in 2008. Improvements in precision in line with those predicted by phantom studies were observed, but the use of fewer technicians during measurement seemed adversely to affect performance. We compared the levels of fluorine observed in people between the two studies and found them to be comparable. The average fluorine concentration in bone was found to be 3  ±  0.3 mg and 3.5  ±  0.4 mg F/g Ca for 2013 and 2008 measurements respectively. Ten people were measured in both studies; the observed average change in bone fluorine in this subgroup was consistent with that predicted by the observation of the relationship between bone fluorine and age in the wider group. In addition, we observed differences in the relationship between bone fluorine level and age between men and women, which may be attributable either to sex or gender differences. The rate of increase in fluorine content for men was found to be 0.096  ±  0.022 mg F/g Ca per year while the rate of increase for women was found to be slightly less than half that of men, 0.041  ±  0.017 mg F/g Ca per year. A discontinuity in the rate of increase in fluorine content with age was observed in women at around age 50. Bone fluorine content was significantly lower ([Formula: see text]) in women age 50 to 59 than in women age 40 to 49, which we suggest may be attributable to bone metabolism changes associated with menopause. We also observed increased fluorine levels in tea drinkers as compared to non-tea drinkers, suggesting tea may be a significant source of exposure in Canada. The rate of increase in fluorine content of the tea drinkers and the non-tea drinkers were found to be 0.127 (± 0.029) and 0.050 (± 0.009) mg F/g Ca per year respectively. Finally, we also obtained twelve bone samples from cadavers' skulls. Neutron activation analysis was used to determine the fluorine levels in these ex vivo samples. The rate of increase of fluorine content versus age for in vivo and ex vivo measurements were found to be 0.078  ±  0.014 and 0.078  ±  0.050 mg F/g Ca per year respectively. Excellent agreement was found between the fluorine levels determined in vivo and ex vivo using the two separate systems, providing confidence in the fluorine concentration data being measured in vivo.

The feasibility of using a (109)Cd γ-ray induced K x-ray fluorescence (K-XRF) system for the in vivo detection of gadolinium (Gd) in bone has been investigated. The K-XRF bone measurement system employs an array of four detectors, and is normally used for the non-invasive study of bone lead levels. The system was used to measure bone simulating phantoms doped with varying levels of gadolinium and fixed amounts of sodium (Na), chlorine (Cl) and calcium (Ca). The detection limits for bare bone phantoms, using a source of activity 0.17 GBq, were determined to be 3.9 ppm and 6.5 ppm (µg Gd per gram phantom) for the Kα1 and Kα2 Gd x-ray peaks, respectively. This leads to an overall detection limit of 3.3 ppm (µg Gd per gram phantom). Layers of plastic were used to simulate overlying soft tissue and this permitted prediction of a detection limit, using the current strength of our radioisotope source, of 6.1 ppm to 8.6 ppm (µg Gd per gram phantom) for fingers with 2-4 mm of overlying tissue. With a new source of activity 5 GBq, we predict that this system could achieve a detection limit of 4-5.6 µg Gd g(-1) Ca. This is within the range of levels (2-30 µg Gd g(-1) Ca) previously found in the bone of patients receiving Gd based contrast imaging agents. The technique is promising and warrants further investigation.

Manganese (Mn) is an essential element for humans, animals, and plants and is required for growth, development, and maintenance of health. Studies show that Mn metabolism is similar to that of iron, therefore, increased Mn levels in humans could interfere with the absorption of dietary iron leading to anemia. Also, excess exposure to Mn dust, leads to nervous system disorders similar to Parkinson's disease. Higher exposure to Mn is essentially related to industrial pollution. Thus, there is a benefit in developing a clean non-invasive technique for monitoring such increased levels of Mn in order to understand the risk of disease and development of appropriate treatments. To this end, the feasibility of Mn measurements with their minimum detection limits (MDL) has been reported earlier from the McMaster group. This work presents improvement to Mn assessment using an upgraded system and optimized times of irradiation and counting for induced gamma activity of Mn. The technique utilizes the high proton current Tandetron accelerator producing neutrons via the (7)Li(p,n)(7)Be reaction at McMaster University and an array of nine NaI (Tl) detectors in a 4 π geometry for delayed counting of gamma rays. The neutron irradiation of a set of phantoms was performed with protocols having different proton energy, current and time of irradiation. The improved MDLs estimated using the upgraded set up and constrained timings are reported as 0.67 μgMn/gCa for 2.3 MeV protons and 0.71 μgMn/gCa for 2.0 MeV protons. These are a factor of about 2.3 times better than previous measurements done at McMaster University using the in vivo set-up. Also, because of lower dose-equivalent and a relatively close MDL, the combination of: 2.0 MeV; 300 μA; 3 min protocol is recommended as compared to 2.3 MeV; 400 μA; 45 s protocol for further measurements of Mn in vivo., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

A (109)Cd K X-ray fluorescence (KXRF) measurement system consisting of four detectors in clover-leaf geometry is a non-invasive, low-radiation-dose method of measuring bone lead concentration. Its high precision in estimating the bone lead content makes it a promising tool for the determination of the low levels of lead currently found in the general population. After developing the clover-leaf geometry system, the system was used for the first time in a major survey in 2008 to measure the lead levels of 497 smelter employees (an occupationally exposed group with high lead levels). Since the delivered effective dose of the bone lead system in clover-leaf geometry is small (on the order of nSv), the technique can be used to measure the bone lead of sensitive populations such as the elderly and children. This detector system was used from 2009 to 2011, in a pilot study that measured the bone lead concentration of 263 environmentally exposed individuals (termed the EG group) residing in Toronto, Ontario, Canada. In this paper, the factors that influence uncertainties in lead content in tibia (cortical bone) and calcaneus (trabecular bone) are discussed based on gender, age, and body mass index (BMI) by using analysis of variance (ANOVA) and multiple linear regression models. Results from the two study groups (the EG group versus the occupationally exposed smelter employees) are compared where appropriate (i.e. for males older than 20). Results from univariate analyses showed that females have higher tibia uncertainty compared to males. We observed significant differences for both calcaneus and tibia uncertainty measures (p < 0.0005) among different age groups, where the uncertainties were highest in the lowest age group (<11 years). Lastly, and perhaps most significantly, we found that the product of source activity and measurement time influenced the precision of measurements greatly, and that this factor alone could account for the higher uncertainties observed for the male cohort of the EG group versus the smelter employees.

Gadolinium (Gd) based contrast agents are routinely used as part of many magnetic resonance imaging (MRI) procedures. The widespread use of these agents and concerns about Gd toxicity, motivated us to develop a monitoring procedure that could non-invasively measure quantitatively potential retention of toxic free Gd in tissues after use of the agent. We have been developing a method to measure Gd painlessly and non-invasively by prompt gamma neutron activation analysis. In this paper we present the results of a pilot study where we show that we can measure Gd, quantitatively in vivo, in the lower leg muscle of 10 participants. A series of three neutron leg scans were performed. The effective radiation dose for a single neutron leg scan was very low, 0.6 µSv, so multiple scans were possible. Calibration phantom and in vivo detection limits were determined to be identical: 0.58 ppm. Gd was not detectable in muscle prior to exposure to the contrast agent Gadovist(®). Gd was detected, at greater than 99% confidence, in 9 participants within 1 h of contrast administration and in 1 participant approximately 3.3 h post-contrast administration. The measured concentrations of Gd ranged from 2.0 to 17.3 ppm (6.9 to 56 uncertainties different from zero). No detectable Gd was measured in any participant in the third neutron scan (conducted 0.7 to 5.9 d post-contrast). The results of this study validate our new measurement technology. This technique could be used as a non-invasive monitoring procedure for exposure and retention of Gd from Gd-based chelates used in MRI.

The overwhelming proportion of the mass of lead (Pb) is stored in bone and the residence time of Pb in bone is much longer than that in other tissues. Hence, in a metabolic model that we used to solve the differential equations governing the transfer of lead between body compartments, three main compartments are involved: blood (as a transfer compartment), cortical bone (tibia), and trabecular bone (calcaneus). There is a bidirectional connection between blood and the other two compartments. A grid search chi-squared minimization method was used to estimate the initial values of lead transfer rate values from tibia (λTB) and calcaneus (λCB) to blood of 209 smelter employees whose bone lead measurements are available from 1994, 1999, and 2008, and their blood lead level from 1967 onwards (depending on exposure history from once per month to once per year), and then the initial values of kinematic parameters were used to develop multivariate models in order to express λTB and λCB as a function of employment time, age, body lead contents and their interaction. We observed a significant decrease in the transfer rate of lead from bone to blood with increasing body lead contents. The model was tested by calculating the bone lead concentration in 1999 and 2008, and by comparing those values with the measured ones. A good agreement was found between the calculated and measured tibia/calcaneus lead values. Also, we found that the transfer rate of lead from tibia to blood can be expressed solely as a function of cumulative blood lead index.

Ten female volunteers were recruited as part of the Ryerson and McMaster University Strontium (Sr) in Bone Research Study to have their bone Sr levels measured as they self-supplemented with Sr supplements of their choice. Of the ten volunteers, nine were suffering from osteopenia and/or osteoporosis. Non-invasive bone Sr measurements were performed using an in vivo x-ray fluorescence (IVXRF) I-125 based system. Thirty minute measurements were taken at the finger and ankle, representing primarily cortical and trabecular bone, respectively. For analysis, the 14.2keV Sr K-alpha peak normalized to the Coherent peak at 35.5keV was used. Baseline readings, representing natural bone Sr levels were acquired since all volunteers had no previous intake of Sr based supplements or medications. Once Sr supplements were started, a 24h reading was taken, followed by frequent measurements ranging from weekly, biweekly to monthly. The longest volunteer participation was 1535days. The mean baseline Sr signal observed for the group was 0.42±0.13 and 0.39±0.07 for the finger and ankle, respectively. After 24h, the mean Sr signal rose to 1.43±1.12 and 1.17±0.51, for the finger and ankle, respectively, representing a statistically significant increase (p=0.0043 & p=0.000613). Bone Sr levels continued to increase throughout the length of the study. However the Sr signal varied widely between the individuals such that after three years, the highest Sr signal observed was 28.15±0.86 for the finger and 26.47±1.22 for the ankle in one volunteer compared to 3.15±0.15 and 4.46±0.36, for the finger and ankle, respectively in another. Furthermore, while it was previously reported by our group, that finger bone Sr levels may plateau within two years, these results suggest otherwise, indicating that bone Sr levels will continue to rise at both bone sites even after 4years of Sr intake., (Copyright © 2014 Elsevier Inc. All rights reserved.)

We previously published a method for the in vivo measurement of bone fluoride using neutron activation analysis (NAA) and demonstrated the utility of the technique in a pilot study of environmentally exposed people. The method involved activation of the hand in an irradiation cavity at the McMaster University Accelerator Laboratory and acquisition of the resultant γ-ray signals in a '4π' NaI(Tl) detector array of nine detectors. In this paper we describe a series of improvements to the method. This was investigated via measurement of hand simulating phantoms doped with varying levels of fluorine and fixed amounts of sodium, chlorine and calcium. Four improvements to the technique were tested since our first publication. The previously published detection limit for phantom measurements using this system was 0.66 mg F/g Ca. The accelerator irradiation and detection facilities were relocated to a new section of the laboratory and one more detector was added to the detection system. This was found to reduce the detection limit (possibly because of better detection shielding and additional detector) to 0.59 mg F/g Ca, a factor of 1.12. A new set of phantoms was developed and in this work we show that they improved the minimum detectable limit for fluoride in phantoms irradiated using neutrons produced by 2.15 MeV protons on lithium by a factor of 1.55. We compared the detection limits previously obtained using a summed signal from the nine detectors with the detection limit obtained by acquiring the spectra in anticoincidence mode for reduction of the disturbing signal from chlorine in bone. This was found to improve the ratio of the detection of fluorine to chlorine (an interfering signal) by a factor of 2.8 and the resultant minimum detection limit was found to be reduced by a factor of 1.2. We studied the effects of changing the timing of γ-ray acquisition. Our previously published data used a series of three 10 s acquisitions followed by a 300 s count. Changing the acquisition to a series of six 5 s acquisitions was found to further improve the detection limit by a factor of 1.4. We also present data showing that if the neutron dose is delivered to the phantom in a shorter time period, i.e. the dose rate is increased and irradiation shortened then the detection limit can be reduced by a further factor of 1.35.The overall improvement in detection limit by employing all of these changes was found to be a factor of 3.9. The technique now has an in phantom detection limit of 0.17 mg F/g Ca compared to a previous detection limit of 0.66 mg F/g Ca. The system can now be tested on human volunteers to see if individuals with diagnosed fluorosis can be distinguished from the general Canadian population using this technique.

Fluorine is an element that can be either beneficial or harmful, depending on the total amount accumulated in the teeth or bones. In our laboratory, we have developed a non-invasive technique for the in vivo measurement of fluoride in bone using neutron activation analysis and performed the first pilot human study. Fluoride in humans is quantified by comparing the γ-ray signal from a person to the γ-ray signal obtained from appropriate anthropomorphic calibration phantoms. An identified problem with existing fluoride phantoms is contamination with aluminum. Aluminum creates an interfering γ-ray signal which, although it can be subtracted out, increases the uncertainty in the measurement and worsens the detection limit. This paper outlines a series of studies undertaken to develop a better calibration phantom for fluorine measurement, which does not have aluminum contamination.

Strontium ranelate is an approved pharmacotherapy for osteoporosis in Europe and Australia, but not in Canada or the United States. Strontium citrate, an alternative strontium salt, however, is available for purchase over-the-counter as a nutritional supplement. The effects of strontium citrate on bone are largely unknown. The study's objectives were 1) to quantify bone strontium accumulation in female Sprague Dawley rats administered strontium citrate (N=7) and compare these levels to rats administered strontium ranelate (N=6) and vehicle (N=6) over 8 weeks, and 2) to verify an in vivo X-ray fluorescence spectroscopy (XRF) system for measurement of bone strontium in the rat. Daily doses of strontium citrate and strontium ranelate were determined with the intention to achieve equivalent amounts of elemental strontium. However, post-hoc analyses of each strontium compound conducted using energy dispersive spectrometry microanalysis revealed a higher elemental strontium concentration in strontium citrate than strontium ranelate. Bone strontium levels were measured at baseline and 8 weeks follow-up using a unique in vivo XRF technique previously used in humans. XRF measurements were validated against ex vivo measurements of bone strontium using inductively coupled plasma mass spectrometry. Weight gain in rats in all three groups was equivalent over the study duration. A two-way ANOVA was conducted to compare bone strontium levels amongst the three groups. Bone strontium levels in rats administered strontium citrate were significantly greater (p<0.05) than rats administered strontium ranelate and vehicle. ANCOVA analyses were performed with Sr dose as a covariate to account for differences in strontium dosing. The ANCOVA revealed differences in bone strontium levels between the strontium groups were not significant, but that bone strontium levels were still very significantly greater than vehicle., (Copyright © 2012 Elsevier Inc. All rights reserved.)

494 smelter employees from New Brunswick participated in a bone lead survey conducted by McMaster University in 2008, using the four element "clover-leaf" geometry germanium detector system. The employees were measured at two different bone sites, tibia and calcaneus, each measurement lasting 30 minutes. Scattered photons, including Pb X-rays, were collected by the germanium detectors located behind the ¹⁰⁹Cd source. A strong positive correlation was observed between tibia and calcaneus lead concentrations. Having been provided with blood lead levels, a cumulative blood lead index (CBLI) was generated. The employees were classified into four groups based on their date of hire, and their CBLI levels were compared to their tibia and calcaneus lead concentrations in the different groups. The slopes of bone Pb versus CBLI varied amongst groups, with those hired earliest showing the steepest slopes. This could be taken to imply a non-linearity in the uptake of Pb by bone from blood. In this paper, the association of the bone lead concentrations versus CBLI has been expressed by a polynomial function for the whole group of employees.

A previously developed in vivo X-ray fluorescence (IVXRF) I-125 based system was used to measure bone strontium levels non-invasively in an osteoporotic female volunteer. The volunteer was recruited in December 2008, as part of the Ryerson and McMaster University Strontium in Bone Research Study and measured at twice weekly, weekly and monthly intervals. Thirty minute measurements were taken at the finger and ankle bone sites, representing primarily cortical and trabecular bone, respectively and the strontium K-alpha X-ray peak at 14.16 keV was used in the analysis. Since the volunteer had no prior history of strontium based medications or supplementation, baseline natural strontium levels were obtained followed by a 24h measurement of first intake of strontium citrate supplements (680 mg Sr/day). While the baseline levels of 0.38 ± 0.05 and 0.39 ± 0.10 for the finger and ankle, respectively, were on par with those previously reported in Caucasians among twenty-two healthy non-supplementing strontium individuals by our group, an increase began to be seen after 24 hrs of 0.62 ± 0.14 and 0.45 ± 0.12 for the finger and ankle, respectively. By 120 h, the increase was statistically significant at 0.68 ± 0.07 and 0.93 ± 0.05, respectively. Further increases occurred within an interval of 90-180 days, with the most recent, after 800 days, at the finger and ankle being 7 and 15 times higher than the initial baseline reading. The intriguing results show bone strontium incorporation and retention follow a pattern, suggesting strontium levels, at least in the ankle, do not plateau within two to three years and will continue to increase over time, as an individual takes strontium supplements. The ability of this IVXRF system to monitor and measure bone strontium levels over time provides a useful diagnostic tool to help gain insight into strontium bone kinetics., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Humans can be exposed to fluorine (F) through their diet, occupation, environment and oral dental care products. Fluorine, at proper dosages, is believed to have positive effects by reducing the incidence of dental caries, but fluorine toxicity can occur when people are exposed to excessive quantities of fluorine. In this paper we present the results of a small pilot in vivo study on 33 participants living in Southwestern Ontario, Canada. The mean age of participants was 45 ± 18 years with a range of 20-87 years. The observed calcium normalized hand-bone-fluorine concentrations in this small pilot study ranged from 1.1 to 8.8 mg F/g Ca. Every person measured in this study had levels of fluorine in bone above the detection limit of the system. The average fluorine concentration in bone was found to be 3.5 ± 0.4 mg F/g Ca. No difference was observed in average concentration for men and women. In addition, a significant correlation (r(2) = 0.55, p < 0.001) was observed between hand-bone-fluorine content and age. The amount of fluorine was found to increase at a rate of 0.084 ± 0.014 mg F/g Ca per year. There was no significant difference observed in this small group of subjects between the accumulation rates in men and women. To the best of our knowledge, this is the first time data from in vivo measurement of fluorine content in humans by neutron activation analysis have been presented. The data determined by this technique were found to be consistent with results from ex vivo studies from other countries. We suggest that the data demonstrate that this low risk non-invasive diagnostic technique will permit the routine assessment of bone-fluorine content with potential application in the study of clinical bone-related diseases. This small study demonstrated that people in Southern Ontario are exposed to fluoride in measureable quantities, and that fluoride can be seen to accumulate in bone with age. However, all volunteers were found to have levels below those expected with clinical fluorosis, and only one older subject was found to have levels comparable with preclinical exposure.

Purpose: Energy dispersive x-ray fluorescence spectroscopy (XRS) measurements were performed on human cadaver index fingers to measure bone strontium content in the presence of intact overlying soft-tissue. This work assesses the feasibility of applying a normalization procedure including soft-tissue correction of x-ray absorption as a means to quantify an ex vivo bone strontium XRS measurement., Methods: Bone strontium measurements were made using an excitation-detection system incorporating an (125)I x-ray excitation source and an Ortec® Ametek-AMT Si(Li) detector in 180° backscatter geometry. Spectral processing was accomplished using an in-house nonlinear least-squares Marquardt fitting routine. Bone strontium was quantified using an egs5 Monte Carlo based x-ray soft-tissue correction algorithm in conjunction with the normalization of strontium x-rays to the coherent scatter peaks of 35.5 keV (125)I γ-rays., Results: Comparison of tissue intact and bare bone finger XRS measurement quantification attempts revealed an overall discrepancy of 18.6% that is attributed primarily to the significant contribution of soft-tissue to coherent scatter of 35.5 keV source γ-rays and to a lesser degree, inconsistencies with the simulated tissue correction model. Work toward the beginnings of an experimentally derived tissue correction model, as a means to validate the simulated model, have been reported. Two observations hinted at a systematic inflation of the observed Kβ peak area. First, strontium concentrations estimated by Kα peak areas were less than the Kβ peak areas by 28.6% (p < 0.0001) and 10.5% (p < 0.001) for tissue intact and bare bone measurements, respectively. Second, the Kα:Kβ x-ray average ratios between tissue corrected (3.61 ± 0.55) and bare bone predicted (4.4 ± 0.4) did not agree (p < 0.0001) and pointed to shortcomings with the current processing treatment of strontium K x-ray peak area extraction. Through finger bone XRS measurements, bone strontium concentration in the Caucasian population was estimated at 95 ± 15 μg Sr/g dry bone., Conclusions: The discrepancies observed: between quantification attempts of tissue corrected and bare bone measurements, the inflated estimates of Kβ relative to Kα peak concentrations and between observed and expected Kα:Kβ ratios, have indicated that shortcomings with the bone strontium coherent normalization and tissue correction procedure exist. Coherent scatter contribution of soft-tissue overlying bone, tissue correction model limitations, and spectra processing issues are all mentioned as sources of observed discrepancies.

Fluorine (F) plays an important role in dental health and bone formation. Many studies have shown that excess fluoride (F(-)) can result in dental or skeletal fluorosis, while other studies have indicated that a proper dosage of fluoride may have a protective effect on bone fracture incidence. Fluorine is stored almost completely in the skeleton making bone an ideal site for measurement to assess long-term exposure. This paper outlines a feasibility study of a technique to measure bone-fluorine non-invasively in the human hand using in vivo neutron activation analysis (IVNAA) via the (19)F(n,γ)(20)F reaction. Irradiations were performed using the Tandetron accelerator at McMaster University. Eight NaI(Tl) detectors arranged in a 4π geometry were employed for delayed counting of the emitted 1.63 MeV gamma ray. The short 11 s half-life of (20)F presents a difficult and unique practical challenge in terms of patient irradiation and subsequent detection. We have employed two simultaneous timing methods to determine the fluorine sensitivity by eliminating the interference of the 1.64 MeV gamma ray from the (37)Cl(n,γ)(38)Cl reaction. The timing method consisted of three counting periods: an initial 30 s (sum of three 10 s periods) count period for F, followed by a 120 s decay period, and a subsequent 300 s count period to obtain information pertaining to Ca and Cl. The phantom minimum detectable limit (M(DL)) determined by this method was 0.96 mg F/g Ca. The M(DL) was improved by dividing the initial timing period into three equal segments (10 s each) and combining the results using inverse variance weighting. This resulted in a phantom M(DL) of 0.66 mg F/g Ca. These detection limits are comparable to ex vivo results for various bones in the adult skeleton reported in the literature. Dosimetry was performed for these irradiation conditions. The equivalent dose for each phantom measurement was determined to be 30 mSv. The effective dose was however low, 35 µSv, which is comparable to other clinical diagnostic tools. The M(DL), relatively low radiation dose and non-invasiveness indicate the suitability of this method for routine in vivo analysis of bone-fluorine content. This prompted us to perform a trial study in human subjects. A preliminary human study on 34 participants was completed, with 33 of the 34 measurements proving to be successful. The in vivo M(DL) based on the improved timing method was determined to be 0.69 mg F/g Ca for the 33 successful human measurements. In our opinion, this technique has been demonstrated to be a suitable method for in vivo assessment of fluorine bone-burden.

Objective: To find the best lead exposure assessment marker for children., Methods: We recruited 11 children, calculated a cumulative blood lead index (CBLI) for the children, measured their concurrent BLL, assessed their development, and measured their bone lead level., Results: Nine of 11 children had clinically significant neurodevelopment problems. CBLI and current blood lead level, but not the peak lead level, were significantly or marginally negatively associated with the full-scale IQ score., Conclusion: Lead exposure at younger age significantly impacts a child's later neurodevelopment. CBLI may be a better predictor of neurodevelopment than are current or peak blood lead levels.

A total of 497 smelter employees from New Brunswick participated in a bone lead survey conducted by McMaster University in 2008 to examine the efficiency of lead exposure control programmes and a four-element 'clover-leaf' geometry detector system. Nearly 42% of the subjects had participated in both the previous surveys performed in 1994 and 1999. After developing the clover-leaf geometry system in 2006, the reliability of the system based on examining the consistency of four detectors and improving the minimum detection limit (MDL) was tested for the first time in 2008 by measuring lead levels of a large population that was occupationally exposed to lead. The Z test was used to study the distribution of the lead concentration calculated based on K(α) and K(β) lead x-rays, where the results were broadly consistent with a normal distribution criterion, with relatively small means and standard deviations of between 1 and 2. The MDL of the clover-leaf geometry system was improved on average for tibia and calcaneus by a factor of 3.1 compared to the 1999 and 1994 surveys in which a conventional system (one detector) was used. Furthermore, by comparing the results of the three mentioned surveys, the 2008 results were found to represent the highest precision.

The feasibility of using the McMaster University in vivo prompt gamma neutron activation analysis system for the detection of gadolinium has been investigated. Phantoms have been developed for the kidney, liver, and the leg muscle. The initial detection limits are determined to be 7.2 ± 0.3 ppm for the kidney, 3.0 ± 0.1 ppm for the liver, and 2.33 ± 0.08 ppm for the lower leg muscle. A few system optimizations have been tested and show significant detection limit reduction from these initial values. The technique is promising and shows feasibility for in vivo studies of gadolinium retention., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

The interpretation of measurements of bone strontium in vivo using energy dispersive x-ray fluorescence spectroscopy is presently hindered by overlying skin and soft-tissue absorption of the strontium x-rays. The use of imaging technologies to measure the overlying soft-tissue thickness at the index finger measuring site might allow correction of the strontium reading to estimate its concentration in bone. An examination of magnetic resonance (MR), computed tomography (CT) and high-frequency ultrasound (US) imaging technologies revealed that 55 MHz US had the smallest range of measurement uncertainty at 3.2% followed by 1 Tesla MR, 25 MHz US, 8 MHz US and CT at 4.3, 5.4, 6.6 and 7.1% uncertainty, respectively. Of these, only CT imaging appeared to underestimate total thickness (p < 0.05). Furthermore, an inter-study comparison on the accuracy of US measurements of the overlying tissue thickness at finger and ankle in nine subjects was investigated. The 8 MHz US system used in prior in vivo experiments was found to perform satisfactorily in a repeat study of ankle measurements, but indicated that finger thickness measurements may have been misread in previous studies by up to 17.7% (p < 0.025). Repeat ankle measurements were not significantly different from initial measurements at 2.2% difference.