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.

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.

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.

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.

In vivo neutron activation study of the short-term kinetic behaviour of sodium and chlorine in the human hand.

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 24Na and 38Cl 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.

Optimization of data analysis for the in vivo neutron activation analysis of aluminum in bone.

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.

A phantom-based feasibility study for detection of gadolinium in bone in-vivo using X-ray fluorescence.

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.

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.

Feasibility of measuring arsenic and selenium in human skin using in vivo x-ray fluorescence (XRF)--a comparison of methods.

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.

Feasibility of measuring selenium in humans using in vivo neutron activation analysis.

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.

Measurements of fluorine in contemporary urban Canadians: a comparison of the levels found in human bone using in vivo and ex vivo neutron activation analysis.

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.

A neutron activation technique for manganese measurements in humans.

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.

A feasibility study to determine the potential of in vivo detection of gadolinium by x-ray fluorescence (XRF) following gadolinium-based contrast-enhanced MRI.

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.

Gadolinium detection via in vivo prompt gamma neutron activation analysis following gadolinium-based contrast agent injection: a pilot study in 10 human participants.

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.

Improvements in an in vivo neutron activation analysis (NAA) method for the measurement of fluorine in human bone.

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.

Design of a phantom equivalent to measure bone-fluorine in a human's hand via delayed neutron activation analysis.

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.

Monitoring bone strontium levels of an osteoporotic subject due to self-administration of strontium citrate with a novel diagnostic tool, in vivo XRF: a case study.

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.

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.