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 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.

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.