Investigating coherent normalization and dosimetry for the 241Am-La K XRF system.

OBJECTIVES: Lanthanum (La) retention in bone has been shown to occur in individuals who are orally administered lanthanum carbonate (LaC), a drug to treat hyperphosphatemia. The breakdown of LaC in the gastrointestinal tract into La3+ and carbonate ions results in residual quantities of La being deposited in bone. We previously reported on a non-invasive x-ray fluorescence (XRF) system that was developed to quantify bone La concentrations and applied it to a series of excised cadaver tibiae. However, given interpatient variability in bone shape and size, differential signal attenuation that occurs in bone and tissue, patient movement and overlying tissue thickness at the measurement site, quantifying bone La concentrations during in vivo measurements in live subjects needs to be investigated further along with the radiation dose associated with the measurement. APPROACH: Coherent normalization was investigated as a function of overlying tissue thickness, source-subject distance and bone radius through Monte Carlo simulation and experimental work. This was accomplished by observing the ratio of the net La K x-ray peak area to the coherently scattered peak area at 59.5 keV. In addition, the dose delivered during a 2000 s measurement was determined using radiochromic film. MAIN RESULTS: The coherent normalization of the La x-ray signal was shown to be independent of overlying tissue thickness, source-subject movement and bone radius, which indicates that this normalization procedure can correct for these factors. The equivalent skin dose and effective dose were 18.0 mSv and 3.2 µSv, respectively for a five-year-old. SIGNIFICANCE: While coherent normalization for the bone lead (Pb) and bone gadolinium (Gd) systems has been shown to be successful, we also report that this normalization procedure can correct for these interpatient variabilities in the in vivo 241Am-La K XRF system.

Ex vivo quantification of lanthanum and gadolinium in post-mortem human tibiae with estimated barium and iodine concentrations using K x-ray fluorescence.

OBJECTIVES: Lanthanum (La) and gadolinium (Gd) are known to deposit in bone of exposed populations, namely those who are orally administered lanthanum carbonate (LaC, La2(CO3)3) or are injected with Gd-based contrast agents, respectively. In this work, bone La and Gd concentrations from the environment and diet were measured using x-ray fluorescence in ten post-mortem human tibiae. As a secondary objective, bone barium (Ba) and iodine concentrations were estimated. APPROACH: Two calibration lines were produced for La and Gd and the minimum detection limits (MDLs) of the system were determined using a 180° irradiation-detection geometry. MAIN RESULTS: The MDLs of the system were 0.4 µg La g-1 bone mineral and 0.5 µg Gd g-1 bone mineral. The mean concentrations were -0.02 ± 0.1 µg La g-1 bone mineral and 0.1 ± 0.2 µg Gd g-1 bone mineral in tibiae. The average Ba and iodine concentrations estimated from the experimental La calibration line and Monte-Carlo derived sensitivity factors were determined to be 3.4 ± 0.8 µg Ba g-1 bone mineral and -0.5 ± 0.3 µg iodine g-1 bone mineral. Since it was discovered that four donors previously received an iodine-based contrast agent, the mean concentrations in these donors was 27.8 ± 28.4 µg iodine g-1 bone mineral. SIGNIFICANCE: The XRF system has determined baseline concentrations of these four heavy metals in trace quantities from natural exposure pathways (with the exception of iodine in four donors). This indicates that the system can measure low levels in ex vivo tibiae samples and can potentially be further developed for in vivo studies involving live subjects who are directly exposed to these metals.

Assessment of the effect of strontium, lead, and aluminum in bone on dual-energy x-ray absorptiometry and quantitative ultrasound measurements: A phantom study.

PURPOSE: Dual-energy X-ray absorptiometry (DXA) is the gold standard technique to measure areal bone mineral density (aBMD) for the diagnosis of osteoporosis. Because DXA relies on the attenuation of photon to estimate aBMD, deposition of bone-seeking metallic elements such as strontium, lead, and aluminum that differ in atomic numbers from calcium can cause inaccurate estimation of aBMD. Quantitative ultrasound (QUS) is another technique available to assess bone health by measuring broadband ultrasound attenuation (BUA), speed of sound (SOS), and an empirically derived quantity called stiffness index (SI). Because the acoustic properties are not prone to significant change due to changes in microscopic atomic composition of bone, it is hypothesized that QUS is unaffected by the presence of bone-seeking elements in the bone. The objective of this study was to investigate the effect of strontium, lead, and aluminum on DXA-derived aBMD and QUS parameters using bone-mimicking phantoms compatible with both techniques. METHODS: Bone-mimicking phantoms were produced by homogeneously mixing finely powdered hydroxyapatite compounds that contain varying concentrations of strontium, lead, or aluminum with porcine gelatin solution. Seven strontium-substituted phantoms were produced with varying molar ratio of Sr/(Sr + Ca) ranging from 0% to 2%. Four lead-doped phantoms and four aluminum-doped phantoms were constructed with the respective analyte concentrations ranging from 50 to 200 ppm. An additional 0 ppm phantom was produced to be used as a baseline for the lead and aluminum phantom measurements. All phantoms had uniform volumetric bone mineral density (vBMD) of 200 mg/cm3 , and were assessed using a Hologic Horizon® DXA device and a Hologic Sahara® QUS device. Furthermore, theoretical aBMD bias for mol/mol% substitution of calcium with the three bone-seeking elements was calculated. RESULTS: Strong positive linear relationship was found between aBMD measured by DXA and strontium concentration (P < 0.001, r = 0.995). From the measurement of lead and aluminum phantoms using DXA, no statistically significant relationship was observed between aBMD and the analyte concentrations. For the QUS system, with an exception of BUA and lead concentration that exhibited statistically significant relationship (P < 0.038, r = 0.899), no statistically significant change was observed in all QUS parameters with respect to the clinically relevant concentration of all three elements. The calculated theoretical aBMD bias induced by 1 mol/mol% substitution of calcium with strontium, lead, and aluminum were 10.8%, 4.6%, and -0.7%, respectively. CONCLUSION: aBMD measured by DXA was prone to overestimation in the presence of strontium, but acoustic parameters measured by QUS are independent of strontium concentration. The deviation in aBMD induced by the clinically relevant concentrations of lead and aluminum under 200 ppm could not be detected using the Hologic Horizon® DXA device. Furthermore, the SI measured by the QUS system was not affected by lead or aluminum concentrations used in this study.

Calibration of the 125I-induced x-ray fluorescence spectrometry-based system of in vivo bone strontium determinations using hydroxyapatite as a phantom material: a simulation study.

OBJECTIVE: The calibration of in vivo x-ray fluorescence systems of bone strontium quantification, based on 125I excitation, is dependent on a coherent normalization procedure. Application of this procedure with the use of plaster of Paris (poP) as a phantom material requires the application of a coherent conversion factor (CCF) to make the calibration functions transferable between the phantom material and human bone. In this work we evaluate, with the use of Monte Carlo simulation, the potential benefit of employing a newly developed hydroxyapatite phantom material into the calibration protocol. APPROACH: Simulations being performed on bare bone phantoms, as the emission spectrum in this case is equivalent to an emission spectrum of an adequately corrected measurement for soft tissue attenuation of emitted strontium signal. We report that the application of hydroxyapatite phantoms does in fact remove the need for a coherent correction factor (CCF). MAIN RESULTS: The newly developed phantoms can thus be used for the calibration of in vivo bone strontium systems removing one step of the calibration protocol. Calibration is, however, limited to cases in which the concentration is relative to the amount of calcium in the specimen, which is, the most useful quantity in a clinical sense. Determining concentrations on a per-mass-of-material basis, that is, a concentration not normalized to the calcium content of the phantom/bone, results in large biases in estimated bone strontium content. SIGNIFICANCE: The use of an HAp phantom material was found to remove the need for a CCF. It was also found that in the case of an incomplete conversion ratio when preparing the phantom material that there would be little effect on the differential coherent cross-section and thereby the coherent normalization-based calibration protocol.