Ana Pejović-Milić

Ultrasound measurements of overlying soft tissue thickness at four skeletal sites suitable for in vivo x-ray fluorescence.

Due to signal attenuation in overlying soft tissue, development of x-ray fluorescence systems to measure low atomic number elements, such as strontium, in human bone required a search for a skeletal site with thin overlying tissue. This paper reports ultrasound measurements of overlying tissue on 10 subjects, at four anatomical sites. The average tissue thickness at the finger was (2.9+/-0.7) mm. The average tissue thicknesses were (3.6+/-0.7) mm, (4.8+/-2.0) mm, and (8.4+/-1.7) mm at forehead, tibia and heel, respectively. Additionally, both parametric and nonparametric approaches to the relationship between body mass index (BMI) and tissue thickness suggest that there is a significant linear correlation between the subjects BMI and overlying tissue at the finger and heel bone. These correlations might be used as a criterion to perform XRF measurements, however a larger data set is required to address these correlations more clearly.

Quantification of bone strontium levels in humans by in vivo x-ray fluorescence

The need for in vivo bone strontium assessment arises because strontium may exert a number of effects on bone, which may be either beneficial or toxic. Measurements discussed here are noninvasive, no sample is taken, nor is there discomfort to patients. The developed source excited x-ray fluorescence system employs a 109Cd source to excite the strontium K x rays, with the source and detector in approximately 90 degree geometry relative to the sample position. The factors affecting the accuracy and minimal detectable limit for bone strontium in vivo measurements are discussed. A system calibration revealed a minimum detectible limit of approximately 0.25 mg Sr/g Ca, which is sufficient for the monitoring of strontium levels in healthy subjects and patients with elevated bone strontium concentrations. Preliminary in vivo measurements in ten healthy subjects at two bone sites (phalanx and tibia) indicated that this system can be applied for cumulative bone strontium estimation while delivering a low effective dose of 80 nSv during the measurement time. Future work will involve attempts to enhance system precision with alternative fluorescing sources and further optimization of the detection system.

Blood lead levels and cumulative blood lead index (CBLI) as predictors of late neurodevelopment in lead poisoned children

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.

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.

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.

Non Tumor Perfusion Changes Following Stereotactic Radiosurgery to Brain Metastases.

PURPOSE To evaluate early perfusion changes in normal tissue following stereotactic radiosurgery (SRS). METHODS Nineteen patients harboring twenty-two brain metastases treated with SRS were imaged with dynamic susceptibility magnetic resonance imaging (DSC MRI) at baseline, 1 week and 1 month post SRS. Relative cerebral blood volume and flow (rCBV and rCBF) ratios were evaluated outside of tumor within a combined region of interest (ROI) and separately within gray matter (GM) and white matter (WM) ROIs. Three-dimensional dose distribution from each SRS plan was divided into six regions: (1) <2 Gy; (2) 2-5 Gy; (3) 5-10 Gy; (4) 10-12 Gy; (5) 12-16 Gy; and (6) >16 Gy. rCBV and rCBF ratio differences between baseline, 1 week and 1 month were compared. Best linear fit plots quantified normal tissue dose-dependency. RESULTS Significant rCBV ratio increases were present between baseline and 1 month for all ROIs and dose ranges except for WM ROI receiving <2 Gy. rCBV ratio for all ROIs was maximally increased from baseline to 1 month with the greatest changes occurring within the 5-10 Gy dose range (53.1%). rCBF ratio was maximally increased from baseline to 1 month for all ROIs within the 5-10 Gy dose range (33.9-45.0%). Both rCBV and rCBF ratios were most elevated within GM ROIs. A weak, positive but not significant association between dose, rCBV and rCBF ratio was demonstrated. Progressive rCBV and rCBF ratio increased with dose up to 10 Gy at 1 month. CONCLUSION Normal tissue response following SRS can be characterized by dose, tissue, and time specific increases in rCBV and rCBF ratio.

Monitoring bone strontium intake in osteoporotic females self-supplementing with strontium citrate with a novel in-vivo X-ray fluorescence based diagnostic tool

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.

Pure hydroxyapatite phantoms for the calibration of in vivo X-ray fluorescence systems of bone lead and strontium quantification.

Plaster of Paris [poP, CaSO4·(1)/(2) H2O] is the standard phantom material used for the calibration of in vivo X-ray fluorescence (IVXRF)-based systems of bone metal quantification (i.e bone strontium and lead). Calibration of IVXRF systems of bone metal quantification employs the use of a coherent normalization procedure which requires the application of a coherent correction factor (CCF) to the data, calculated as the ratio of the relativistic form factors of the phantom material and bone mineral. Various issues have been raised as to the suitability of poP for the calibration of IVXRF systems of bone metal quantification which include its chemical purity and its chemical difference from bone mineral (a calcium phosphate). This work describes the preparation of a chemically pure hydroxyapatite phantom material, of known composition and stoichiometry, proposed for the purpose of calibrating IVXRF systems of bone strontium and lead quantification as a replacement for poP. The issue with contamination by the analyte was resolved by preparing pure Ca(OH)2 by hydroxide precipitation, which was found to bring strontium and lead levels to <0.7 and <0.3 μg/g Ca, respectively. HAp phantoms were prepared from known quantities of chemically pure Ca(OH)2, CaHPO4·2H2O prepared from pure Ca(OH)2, the analyte, and a HPO4(2-) containing setting solution. The final crystal structure of the material was found to be similar to that of the bone mineral component of NIST SRM 1486 (bone meal), as determined by powder X-ray diffraction spectrometry.

The use of teeth as the site for the in vivo or ex vivo quantification of skeletal strontium by energy-dispersive X-ray fluorescence spectrometry: A feasibility study

The use of an energy-dispersive X-ray fluorescence spectrometry (EDXRF) system equipped with an 125I source was validated for in vivo and ex vivo quantification of strontium in human teeth. The mean concentration of enamel strontium for an area with a high influx of immigration (Toronto, Ontario, Canada) is also reported. It was found that the mass attenuation of the strontium and calcium X-rays allows for a probing depth of 1.8 mm (Sr Kα) allowing the front central incisors to act as the site for the in vivo or ex vivo quantification of strontium as well as for molars to be used ex vivo for the quantification of enamel strontium. The calcium signal for all teeth studied (n = 42) was found to have a relative standard deviation of 5.7% which allowed for successful normalization of the strontium signal to that of calcium. Validation of the EDXRF method was performed on human molars (enamel thickness of (1.9 ± 0.7) mm, p < 0.05), by graphite furnace atomic absorption spectrometry (GFAAS). The EDXRF method was found to produce equivalent strontium determinations to that of GFAAS (p < 0.05). Our results also demonstrate that for a sample from a large metropolitan area, the fresh enamel strontium concentrations range from 42–301 ppm with a mean strontium concentration of (169 ± 80) ppm (p < 0.05).

Monitoring the photographic process, degradation and restoration of 21st century Daguerreotypes by wavelength-dispersive X-ray fluorescence spectrometry

This study applied wavelength-dispersive X-ray fluorescence spectrometry (WDXRF), with its high spectral resolution, to monitor the photographic process, tarnishing and restoration of pristine Daguerreotypes made in the traditional 19th century fashion. The elemental changes upon restoration via thiourea treatment, were evaluated and compared to a method based on bulk electrolysis. The WDXRF system was found to successfully resolve all lines of interest including in the mercury-bromine-gold region. Sulfur, one of the main components of tarnish, was removed efficiently from the surface of the Daguerreotype when restored by electro-cleaning. Restoration by thiourea immersion removed sulfur from the surface of the Daguerreotype to a point at which the residual sulfur was equivalent in content to the residue left after gilding (i.e. from thiosulfate). Thiourea treatment was found to remove a significant amount of gold from the surface of the Daguerreotype, which may explain the sometimes observed dullness imparted to the Daguerreotype after restoration with thiourea. Also, Daguerrian measles were found to accumulate on thiourea treated plates versus those cleaned by electro-cleaning which ultimately negatively imparts further artefacts to the image after restoration.