Iron overload conditions are a prevalent issue in global healthcare that require the accurate monitoring of iron levels to effectively provide treatment. X-ray fluorescence has emerged as a candidate for a point-of-care measurement tool for the detection of trace elements in vivo. This study explores the feasibility of a portable in vivo x-ray fluorescence (IVXRF) instrument using 125I as a point-of-care device in measuring skin iron levels. The system was calibrated using iron-doped water phantoms for various physiologically-applicable iron concentrations. Measurements were conducted on ex vivo rat skin samples (n = 34), which were then compared to a benchmark laboratory-based XRF system. Monte Carlo modelling using MCNP 6.2 was used to simulate the system in different conditions and provide an estimate of the radiation dose of the system on soft tissue. The R2 value for the calibration line of iron concentration in ppm to normalized iron signal was determined to be 0.985 (p < 0.01). For a measurement period of 1800 s real-time, the minimum detectable limit (MDL) of the system is 3.86 ± 0.06 ppm of iron. The R2 value for the linear regression between the IVXRF and benchmark XRF system normalized iron signals was 0.731 (p < 0.01). The R2 value for the linear regression between the IVXRF normalized iron signal and sample injected iron dose was 0.719 (p < 0.01), meaning the system can distinguish between different iron levels in rat skin. From the Monte Carlo simulations, the expected effective dose contribution from the IVXRF system is 101.68 ± 0.03 nSv. The IVXRF system was shown to accurately measure iron concentrations in ex vivo rat skin samples within the iron concentration ranges found within healthy and iron-overloaded patients. Further work shall be conducted to validate the system in in vivo applications. / Thesis / Master of Science (MSc) / Iron overload is a prevalent issue in healthcare, with many individuals experiencing detrimental symptoms, such as organ damage and heart failure. Modern treatment significantly improves quality of life but must be continuously monitored. This thesis covers the development of a non-invasive, cost-effective, and accurate system that can measure skin iron levels in patients to ensure effective monitoring. The results from this thesis suggest that the system can be used for clinical use to measure patient skin iron levels. It can theoretically measure iron in patients with normal and elevated iron levels. Simulation work suggests that the system will lead to negligible risk from radiation exposure. While this thesis and its findings support the feasibility of the system, further work is required before clinical implementation of the device.

The health impact of iron (Fe) deficiency or excess on the human body can be severe. Existing clinical methods for assessing body Fe levels have limitations. This thesis focuses on the potential of measuring skin Fe concentrations using X-ray Fluorescence (XRF) to assess body Fe levels. A portable XRF instrument based on a silicon drift detector has been developed. The instrument was calibrated using water-based phantoms, achieving a minimum detection limit of 1.35 ± 0.35 ppm (Fe) with a measurement time of 1800 s and a radiation dose of 1.1 ± 0.1 mSv to the skin surface. The system accuracy was tested by measuring the skin Fe concentrations in 10 pig skin samples that were not loaded with Fe. The measured pig skin Fe ranged from approximately 8 to 14 ppm with an average value of 11 ppm. The XRF measurements were found to compare well with the results from Inductively Coupled Plasma Mass Spectroscopy (ICP-MS) analysis of the same skin samples. The mean difference between the Fe levels as assessed by XRF and ICP-MS was not significant, measuring at 2.5 ± 4.6 ppm. Synchrotron µXRF mapping of 25 μm thick pig skin sections at a spatial resolution of 20 µm revealed Fe ‘hot spots’ through the skin, predominantly in the dermis, that were attributed to small blood vessels. The synchrotron map also showed that the Fe distribution in the skin peaks near the outer skin surface. Measurements by the system of this skin distribution were modelled using the Monte Carlo code EGS5 and indicated that if a highly elevated Fe layer is present at the surface, correction factors may be necessary for accurate estimation of skin surface Fe levels by the XRF system. The performance of the system was tested using rat skin samples obtained from animals dosed in vivo with varying amounts of Fe. The system was able to distinguish between skin samples from normal rats and rats dosed with 80 mg Fe2+ and between rats dosed with 80 mg Fe2+ and 160 mg Fe2+ (p = 0.001 and p=0.002, respectively). The instrument also exhibited a significant linear relationship between the measured rat skin Fe concentration and rat Fe dose (R2 = 0.84, p < 0.0001). Furthermore, the measurements were validated against a laboratory XRF system, a bulk tissue measurement system (R2 = 0.85, p < 0.0001). Overall, the work in this thesis highlights the promise of using portable XRF for precise and non-intrusive measurement of skin Fe levels in both Fe overload and Fe deficiency conditions. / Thesis / Doctor of Philosophy (PhD)

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