Date of Award

8-2016

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Health Sciences

First Advisor

Linda H. Nie

Committee Chair

Linda H. Nie

Committee Member 1

Keith Stantz

Committee Member 2

Marc Weisskopf

Committee Member 3

Wei Zheng

Abstract

Lead (Pb) is a toxicant well known for its effects on almost every organ system in the body. Pb use in industry has declined since removal of Pb from gasoline, but many developing countries still have significant use of Pb. Exposure to Pb has been linked with diseases causing neurodegeneration and thus have lasting effects long after the initial exposure. Another metal, strontium (Sr), has been linked with bone disease in particular situations and shown to have uses in treating osteoporosis as a supplement. However, there are no studies of the effects of Sr using a meaningful biomarker. The most commonly used biomarkers for Pb and Sr exposures are blood Pb and Sr; however, blood tests are unable to identify long-term exposure levels due to the short half-life of these metals in blood. Bone stores of Pb and Sr have a half-life of years to decades and serve as a biomarker of long-term exposure. X-ray fluorescence has been used to measure bone Pb and Sr. However, current systems have limitations with radioisotope sources, bulky equipment, and long measurement times. A portable XRF device capable of measurement of bone Pb and Sr, overcomes the limitation of the current systems and has been developed in this work. The detection limit of the portable XRF for bone Pb and Sr was found to be 11 ppm and 5 ppm respectively at 5 mm of skin thickness. The portable XRF will have limitations of measurement based on an individual’s skin thickness. The device was calibrated using standard phantoms and validated with in-lab samples, which demonstrated good agreement between KXRF and portable XRF measurements with strong correlations between goat bone, cadaver bone, and phantom measurements. In a population study of Pb poisoned children the portable XRF was further validated and a significant correlation between KXRF measured bone Pb and portable XRF measured bone Pb was identified; however, the device had limitations based on anatomical differences unaccounted for in children from our calibration. Adaptations of our calibration to account for the differences in children’s bone can be used to further improve on the results we obtained. Pb biokinetics was studied in these children, and the blood Pb half-life in the children was calculated to be about 10 days, which is much short than the 30 day half-life identified for adults. Bone Sr was measured in these children and a significant correlation with age was identified, indicating the Sr accumulates in bone. A novel high-energy x-ray tube based KXRF measurement system was tested for its feasibility of in vivo measurement of metals in bone using Monte Carlo (MC) simulation. The novel system shows a combination of the advantages of the portable XRF with a smaller scale device, x-ray tube source, and room temperature detector, as well as the advantages of the KXRF of minimal soft tissue signal degradation with more applicability to a wider range of populations. This device, with an optimized x-ray tube and uranium target of 0.056 mm, was found to have a detection limit for bone Pb measurement of about 3.6 ppm and could be adapted for measurements of multiple metals

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