Investigation of the accuracy of a portable109Cd XRF system for the measurement of iron in skin.

We have previously reported the design of a portable109Cd x-ray fluorescence (XRF) system to measure iron levels in the skin of patients with either iron overload disease, such as thalassemia, or iron deficiency disease, such as anemia. In phantom studies, the system was found to have a detection limit of 1.35µg Fe per g of tissue for a dose of 1.1 mSv. However, the system must provide accurate as well as precise measurements of iron levels in the skin in order to be suitable for human studies. The accuracy of the system has been explored using several methods. First, the iron concentrations of ten pigskin samples were assessed using both the portable XRF system and ICP-MS, and the results were compared. Overall, it was found that XRF and ICP-MS reported average values for iron in skin that were comparable to within uncertainties. The mean difference between the two methodologies was not significant, 2.5 ± 4.6µg Fe per g. On this basis, the system could be considered accurate. However, ICP-MS measurements reported a wider range of values than XRF, with two individual samples having ICP-MS results that were significantly elevated (p < 0.05) compared to XRF. SynchrotronµXRF maps of iron levels in pigskin were acquired on the BioXAS beam line of the Canadian Light Source. TheµXRF maps indicated two important features in the distribution of iron in pigskin. First, there were small areas of high iron concentration in the pigskin samples, that were predominantly located in the dermis and hypodermis at depths greater than 0.5 mm. Monte Carlo modelling using the EGS 5 code determined that if these iron 'hot spots' were located towards the back of the skin at depths greater than 0.5 mm, they would not be observed by XRF, but would be measured by ICP-MS. These results support a hypothesis that iron levels in the two samples that reported significantly elevated ICP-MS results compared to XRF may have had small blood vessels at the back of the skin. Second, the synchrotronµXRF maps also showed a narrow (approximately 100µm thick) layer of elevated iron at the surface of the skin. Monte Carlo models determined that, as expected, the XRF system was most sensitive to these skin layers. However, the simulations found that the XRF system, when calibrated against homogenous water-based phantoms, was found to accurately measure average iron levels in the skin of normal pigs despite the greater sensitivity to the surface layer. The Monte Carlo results further indicated that with highly elevated skin surface iron levels, the XRF system would not provide a good estimate of average skin iron levels. The XRF estimate could, with correction factors, provide a good estimate of the iron levels in the surface layers of skin. There is limited data on iron distribution in skin, especially under conditions of disease. If iron levels are elevated at the skin surface by diseases including thalassemia and hemochromatosis, this XRF device may prove to be an accurate clinical tool. However, further data are required on skin iron distributions in healthy and iron overload disease before this system can be verified to provide accurate measurements.

Feasibility of a109Cd-based portable XRF device for measuring skin iron concentration in anaemic andß-Thalassaemic patients.

Iron is an essential element vital for growth and development. The severe effects on the body due to iron deficiency or overload have prompted sustained research into accuratein vivoiron measurement techniques for the past several decades. X-ray fluorescence (XRF) analysis of iron in the body has been investigated in this work because of the non-invasive nature of the technique. A system has been designed using a silicon drift detector to measure the low-energy iron Kαx-rays excited in the samples by the silver x-rays from109Cd of energy 22 keV and 25 keV. The source is contained within a tantalum shielding cap designed to reduce the spectral background. The system was calibrated against 3D printed polylactic acid (PLA) phantoms filled with solutions of iron at various concentrations. The iron x-ray signals were normalized to a nickel x-ray signal which improved the system's reproducibility. The 3D phantoms and normalisation resulted in a linear calibration line (p < 0.001 and r2 > 0.999). For a real-time measurement of 1800 s, the minimum detectable limit for the system was measured to be 1.35 ± 0.35 ppm which is achieved with a low radiation dose of 1.1 mSv to the skin surface. This low detection limit and low dose mean the system is feasible for application to human measurements in both iron deficiency and overload disease. The system will proceed to post-mortem validation studies prior toin vivosystem efficacy testing.