Bone aluminum measured in miners exposed to McIntyre powder.

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.

Ex vivo evaluation of a coherent normalization procedure to quantify in vivo finger strontium XRS measurements.

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 Kß peak area. First, strontium concentrations estimated by Kα peak areas were less than the Kß 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:Kß 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 Kß relative to Kα peak concentrations and between observed and expected Kα:Kß 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.

Opportunities to improve the in vivo measurement of manganese in human hands.

Manganese (Mn) is an element which is both essential for regulating neurological and skeletal functions in the human body and also toxic when humans are exposed to excessive levels. Its excessive inhalation as a result of exposure through industrial and environmental emissions can cause neurological damage, which may manifest as memory deficit, loss of motor control and reduction in the refinement of certain body motions. A number of clinical studies demonstrate that biological monitoring of Mn exposure using body fluids, particularly blood, plasma/serum and urine is of very limited use and reflect only the most recent exposure and rapidly return to within normal ranges. In this context, a non-invasive neutron activation technique has been developed at the McMaster University accelerator laboratory that could provide an alternative to measure manganese stored in the bones of exposed subjects. In a first pilot study we conducted recently on non-exposed human subjects to measure the ratio of Mn to Ca in hand bones, it was determined that the technique needed further development to improve the precision of the measurements. It could be achieved by improving the minimum detection limit (MDL) of the system from 2.1 microg Mn/g Ca to the reference value of 0.6 microg g(-1) Ca (range: 0.16-0.78 microg Mn/g Ca) for the non-exposed population. However, the developed procedure might still be a suitable means of screening patients and people exposed to excessive amounts of Mn, who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. To improve the MDL of the technique to the expected levels of Mn in a reference population, the present study investigates further optimization of irradiation conditions, which includes the optimal selection of proton beam energy, beam current and irradiation time and the effect of upgrading the 4pi detection system. The maximum local dose equivalent that could be given to the hand as a result of irradiation was constrained to be less than 150 mSv as opposed to the previously imposed dose equivalent limit of 20 mSv. A maximum beam current, which could be delivered on the lithium target to produce neutrons, was restricted to 500 microA. The length of irradiation intervals larger than 10 min, was considered inconvenient and impractical to implement with Mn measurements in humans. To fulfil the requirements for developing a protocol for in vivo bone Mn measurements, a revised estimate of the dose equivalent has been presented here. Beam energy of 1.98 MeV was determined to be optimal to complete the irradiation procedure within 10 min using 500 microA beam current. The local dose equivalent given to hand was estimated as 118 mSv, which is lower by a factor of 1.5 compared to that of 2.00 MeV. The optimized beam parameters are expected to improve the currently obtained detection limit of 2.1 microg Mn/g Ca to 0.6 microg Mn/g Ca. Using this dose equivalent delivered to the central location of the hand, the average dose equivalent to the hand of 74 mSv and an effective dose of approximately 70 microSv will be accompanying the non-invasive, in vivo measurements of bone Mn, which is little over the chest radiograph examination dose.

Calibration of (109)Cd KXRF systems for in vivo bone lead measurements: weighted least-squares regression with different weighting functions.

The use of iteratively reweighted least squares (IRLS) has recently been described as an alternative to ordinary least squares with heteroscedastic data, in the calibration of (109)Cd KXRF systems for in vivo bone lead measurements. This work addresses the use of weighted least squares (WLS) with two different weighting functions and no iteration, with that same data set. The functions are defined as the inverse of the variance of observed ratios of lead to coherent peak amplitudes and the inverse of the square of the error reported by the Marquardt fitting program for these ratios. The results show that if no iteration is implemented when using WLS, then the two weighting functions are highly inefficient in homogenizing the residual variance. Moreover, both methods estimate much more imprecise calibration intercepts and slopes than did the IRLS method. Work is in progress to investigate the implementation of IRLS with these weighting functions, with the focus on the selection of the best function for residuals to be used in each iteration stage.

Calibration of (109)Cd KXRF systems for in vivo bone lead measurements: the guiding role of the assumptions for least-squares regression in practical problem solving.

The use of least-squares regression to probe the level of lead contamination of plaster of Paris standards in the calibration of (109)Cd KXRF systems for bone lead measurement, as well as the use of iteratively reweighted least-squares (IRLS) in the case of violation of the assumptions for ordinary least-squares (OLS), is discussed here. One common violation is non-uniform residual variance, which makes the use of OLS inappropriate due to strong influence of points with large variance on the calibration line and variance of the slope and intercept. Comparison between OLS and IRLS in that case showed that IRLS estimates of the intercept are significantly smaller and more precise than OLS estimates, while a less marked increase in the calibration slope is observed when IRLS is used. Moreover, OLS underestimates bone lead concentrations at low levels of lead exposure and overestimates those concentrations at higher levels. These discrepancies are smaller in magnitude than the measurement uncertainty of conventional systems, except for high concentrations. For the newly developed cloverleaf systems, the suggested differences at bone lead concentrations below 17 ppm are comparable to the minimum detection limit, but are larger than the measurement uncertainty for bone lead concentrations above 60 ppm.

In vivo measurement of bone aluminum in population living in southern Ontario, Canada.

The harmful biological effect of excessive aluminum (Al) load in humans has been well documented in the literature. Al stored in bone, for instance due to dialysis treatment or occupational exposure, can interfere with normal bone remodeling leading to osteodystrophy, osteoarthritis, or osteomalacia. On the other hand, the relationship between chronic Al exposure and the risk of Alzheimer's disease remains controversial. In this work, the feasibility of in vivo neutron activation analysis (IVNAA) for measuring Al levels in the human hand bone, using the thermal neutron capture reaction 27Al(n, gamma)28 Al, is reported. This noninvasive diagnostic technique employs a high beam current Tandetron accelerator based neutron source, an irradiation/shielding cavity, a 47pi NaI(Tl) detector system, and a new set of hand bone phantoms. The photon spectra of the irradiated phantom closely resemble those collected from the hands of nonexposed healthy subjects. A protocol was developed using the newly developed hand phantoms, which resulted in a minimum detectable limit (MDL) of 0.29 mg Al in the human hand. Using the ratio of Al to Ca as an index of Al levels per unit bone mass, the MDL was determined as 19.5 +/- 1.5 microg Al/g Ca, which is within the range of the measured levels of 20-27 microg Al/g Ca [ICRP Report of the Task Group on Reference Man, Publication 23 (Pergamon, Oxford, 1975)] found in other in vivo and in vitro studies. Following the feasibility studies conducted with phantoms, the diagnostic technique was used to measure Al levels in the hand bones of 20 healthy human subjects. The mean hand bone Al concentration was determined as 27.1 +/- 16.1 (+/-1 SD) microg Al/g Ca. The average standard error (1sigma) in the Al/Ca is 14.0 microg Al/g Ca, which corresponds to an average relative error of 50% in the measured levels of Al/Ca. These results were achieved with a dose equivalent of 17.6 mSv to a hand and an effective dose of 14.4 microSv. This effective dose is approximately half of that received in a chest radiograph examination. It is recommended to investigate the use of the bone Al IVNAA diagnostic technique for in vivo measurements of patients with documented overload of Al in bone.

In vivo assessment of magnesium status in human body using accelerator-based neutron activation measurement of hands: a pilot study.

Magnesium (Mg) is an element essential for many enzymatic reactions in the human body. Various human and animal studies suggest that changes in Mg status are linked to diseases such as cardiac arrhythmia, coronary heart disease, hypertension, premenstrual syndrome, and diabetes mellitus. Thus, knowledge of Mg levels in the human body is needed. A direct measurement of human blood serum, which contains only 0.3% of the total body Mg, is generally used to infer information about the status of Mg in the body. However, in many clinical situations, Mg stored in large levels, for example in bones, muscles, and soft tissues, needs to be monitored either to evaluate the efficacy of a treatment or to study the progression of diseases associated with the deficiency of total body Mg. This work presents a feasibility study of a noninvasive, in vivo neutron activation analysis (IVNAA) technique using the 26Mg (n, gamma) 27Mg reaction to measure Mg levels in human hands. The technique employs the McMaster University high beam current Tandetron accelerator hand irradiation facility and an array of eight NaI (T1) detectors arranged in a 4 pi geometry for delayed counting of the 0.844 and 1.014 MeV gamma rays emitted when 27Mg decays in the irradiated hand. Mg determination in humans using IVNAA of hands has been demonstrated to be feasible, with effective doses as low as one-quarter of those delivered in chest x rays. The overall experimental uncertainty in the measurements is estimated to be approximately 5% (1 sigma). The results are found to be in the range of the in vitro measurements reported for other cortical bones collected from different sites of the human skeleton, which confirms that this technique mainly provides a measure of the amount of Mg in hand bones. The average concentration of Mg determined in human hands is 10.96 +/- 1.25 (+/- 1 SD) mg Mg/g Ca. The coefficient of variation (11%) observed in this study is comparable with or lower than several studies using in vitro measurements reported in the literature and therefore allows for a quantitative intersubject comparison, even if to a limited extent. The features of the developed technique such as its simplicity, rapidity, accuracy, robustness, noninvasive nature, and very effective use of radiation doses, present the technique as a viable diagnostic tool available for trial in a clinical environment.

Quantification of manganese in human hand bones: a feasibility study.

Manganese is both an essential element to human health and also toxic when humans are exposed to excessive levels, particularly by means of inhalation. Biological monitoring of manganese exposure is problematic. It is subject to homeostasis; levels in blood (or serum/plasma) reflect only the most recent exposure and rapidly return to within normal ranges, even when there has been a temporary excursion in response to exposure. In this context, we have been developing a non-invasive technique for measurement of manganese stored in bone, using in vivo neutron activation analysis. Following preliminary feasibility studies, the technique has been enhanced by two significant infrastructure advances. A specially designed irradiation facility serves to maximize the activation of manganese with respect to the dose of ionizing radiation. Secondly, an array of eight NaI(Tl) crystals provides a detection system with very close to 4 pi geometry. This feasibility study, using neutron activation analysis to measure manganese in the bones of the hand, takes two features into account. Firstly, there is considerable magnesium present in the bone and this produces a spectral interference with the manganese. The 26 Mg(n,gamma)27 Mg reaction produces gamma -rays of 0.843 MeV from the decay of 27 Mg, which interfere with the 0.847 MeV gamma -rays from the decay of 56 Mn,produced by the 55 Mn(n,gamma)56 Mn reaction. Secondly, this work provides estimates of the levels of manganese to be expected in referent subjects. A revised estimate has been made from the most recent literature to explore the potential of the technique as a suitable means of screening patients and people exposed to excessive amounts of Mn who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. This report presents the enhancements to the neutron activation system, by which manganese can be measured, which resulted in a detection limit in the hand of human subjects of 1.6 microg/g Ca. It also provides a revised estimate of expected referent levels of manganese in bone, now estimated to be 0.63 microg/g Ca and highlights the extent to which technical improvements will be required to further extend the application of the technique for in vivo measurements in non-exposed human subjects.

Coherent normalization of finger strontium XRF measurements: feasibility and limitations.

A non-invasive in vivo x-ray fluorescence (XRF) method of measuring bone strontium concentrations has previously been reported as a potential diagnostic tool able to detect strontium concentration in the finger and ankle bones. The feasibility of coherent normalization for (125)I-source-based finger bone strontium x-ray fluorescence (XRF) measurements is assessed here by theoretical considerations and Monte Carlo simulations. Normalization would have several advantages, among which are the correction for the signal attenuation by the overlying soft tissue, and intersubject variability in the bone size and shape. The coherent normalization of bone strontium XRF measurements presents several challenges dictated by the behaviour of the coherent cross section and mass attenuation coefficient at the energies involved. It was found that the coherent normalization alone with either 22.1 keV or 35.5 keV photons was not successful in correcting for the overlying soft tissue attenuation. However, it was found that the coherent peak at 35.5 keV was able to correct effectively for variability in the finger bone size between people. Thus, it is suggested that, if the overlying soft tissue thickness can be obtained by means of an independent measurement, the 35.5 keV peak can be used to correct for the bone size, with an overall accuracy of the normalization process of better than 10%.

A preliminary study for non-invasive quantification of manganese in human hand bones.

Manganese (Mn) is a nutrient essential for regulating neurological and skeletal functions in the human body, but it is also toxic when humans are excessively exposed to Mn. Blood (or serum/plasma) and other body fluids reflect only the most recent exposure and rapidly return to within normal ranges, even when there has been a temporary excursion in response to exposure. In this context, we have been developing a non-invasive measurement of Mn stored in bone, using in vivo neutron activation analysis. Following feasibility studies, a first pilot study, using neutron activation analysis to measure Mn in the bones of the hand of ten healthy male human subjects, was conducted with the approval of the concerned research ethics boards. The participants of this study had no known history of exposure to Mn. Two volunteers were excluded from this study due to technical problems with their measurements. The inverse variance weighted mean value of Mn/Ca for the participants of this study is 0.12+/-0.68 microg Mn/g Ca which is comparable within uncertainties with the estimated range of 0.16-0.78 microg Mn/g Ca and mean value of 0.63+/-0.30 microg Mn/g Ca derived from cadaver data. It is recommended to investigate the use of the diagnostic technique for in vivo measurements of workers exposed occupationally to excessive amounts of Mn who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. The technique needs further development to improve the precision of in vivo measurements in the non-exposed population.

Random left censoring: a second look at bone lead concentration measurements.

Bone lead concentrations measured in vivo by x-ray fluorescence (XRF) are subjected to left censoring due to limited precision of the technique at very low concentrations. In the analysis of bone lead measurements, inverse variance weighting (IVW) of measurements is commonly used to estimate the mean of a data set and its standard error. Student's t-test is used to compare the IVW means of two sets, testing the hypothesis that the two sets are from the same population. This analysis was undertaken to assess the adequacy of IVW in the analysis of bone lead measurements or to confirm the results of IVW using an independent approach. The rationale is provided for the use of methods of survival data analysis in the study of XRF bone lead measurements. The procedure is provided for bone lead data analysis using the Kaplan-Meier and Nelson-Aalen estimators. The methodology is also outlined for the rank tests that are used to determine whether two censored sets are from the same population. The methods are applied on six data sets acquired in epidemiological studies. The estimated parameters and test statistics were compared with the results of the IVW approach. It is concluded that the proposed methods of statistical analysis can provide valid inference about bone lead concentrations, but the computed parameters do not differ substantially from those derived by the more widely used method of IVW.

In vivo study of an x-ray fluorescence system to detect bone strontium non-invasively.

An x-ray fluorescence (XRF) system using 125I as the source was developed to measure strontium in bone in vivo. As part of an in vivo pilot study, 22 people were measured at two bone sites, namely the index finger and the tibial ankle joint. Ultrasound measurements were used to obtain the soft tissue thickness at each site, which was necessary to correct the signal for tissue attenuation. For all 22 people, the strontium peak was clearly distinguishable from the background, proving that the system is able to measure Sr in vivo in people having normal bone Sr levels. Monte Carlo simulations were carried out to test the feasibility and the limitations of using the coherently scattered peak at 35.5 keV as a means to normalize the signal to correct for the bone size and shape. These showed that the accuracy of the normalized Sr signal when comparing different people is about 12%. An interesting result arising from the study is that, in the measured population, significantly higher measurements of bone Sr concentration were observed in continental Asian people, suggesting the possibility of a dietary or race dependence of the bone Sr concentration or a different bone biology between races.

Dosimetric characterization of the irradiation cavity for accelerator-based in vivo neutron activation analysis.

A neutron irradiation cavity for in vivo activation analysis has been characterized to estimate its dosimetric specifications. The cavity is defined to confine irradiation to the hand and modifies the neutron spectrum produced by a low energy accelerator neutron source to optimize activation per dose. Neutron and gamma-ray dose rates were measured with the microdosimetric technique using a tissue-equivalent proportional counter at the hand irradiation site and inside the hand access hole. For the outside of the cavity, a spherical neutron dose equivalent meter and a Farmer dosemeter were employed instead due to the low intensity of the radiation field. The maximum dose equivalent rate at the outside of the cavity was 2.94 microSv/100 microA min, which is lower by a factor of 1/2260 than the dose rate at the hand irradiation position. The local dose contributions from a hand, an arm and the rest of a body to the effective dose rate were estimated to be 1.73, 0.782 and 2.94 microSv/100 microA min, respectively. For the standard irradiation protocol of the in vivo hand activation, 300 microA min, an effective dose of 16.3 microSv would be delivered.

Monte Carlo simulation of trabecular bone remodelling and absorbed dose coefficients for tritium and 14C.

A Monte Carlo simulation of multiple trabecular bone cavities in adult bone was developed and the absorbed radiation dose factors evaluated for 3H and 14C. The model was developed to assess the dose from radionuclide uptake in quiescent bone, but also the effects of temporal changes in bone turnover by incorporating bone-modelling units (BMU). Absorbed dose fractions were calculated for target regions that include the endosteal layer where radiation-sensitive stem cells in bone marrow are considered to reside preferentially. There were large differences in the absorbed fractions for two types of bone surface, quiescent and forming. Tritium in quiescent bone results in a dose to the endosteum about 20 times that for the same activity in forming bone surface irradiating osteoblasts. When the quiescent bone surface source was extended from an infinitely thin layer to a more realistic 1 microm thick, the tritium absorbed fractions for endosteum and red marrow targets fell by more than 2-fold.

Coherent normalization for in vivo measurements of gadolinium in bone.

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.

Performance comparison of two Olympus InnovX handheld x-ray analyzers for feasibility of measuring arsenic in skin in vivo - Alpha and Delta models.

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 ~7×10-3µSv respectively for the Alpha and (15±4) mSv and ~8×10-3µSv 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 mSv1/2, compared to (4.4±0.5) ppm mSv1/2 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.

The decrease in population bone lead levels in Canada between 1993 and 2010 as assessed by in vivo XRF.

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.

Age and sex influence on bone and blood lead concentrations in a cohort of the general population living in Toronto.

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 109Cd 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.

Confirming improved detection of gadolinium in bone using in vivo XRF.

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.

Modeling elemental strontium in human bone based on in vivo x-ray fluorescence measurements in osteoporotic females self-supplementing with strontium citrate.

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.