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In vivo detection of gadolinium by prompt gamma neutron activation analysis: An investigation of the potential toxicity of gadolinium-based contrast agents used in MRI

<p>This thesis describes the development of a method to measure <em>in vivo</em> gadolinium (Gd) content by prompt gamma neutron activation analysis (PGNAA). PGNAA is a quantitative measurement technique that is completely non-invasive. Gadolinium has the highest thermal neutron capture cross section of all the stable elements. Gadolinium-based contrast agents are widely used in magnetic resonance imaging (MRI). The primary intention of this work is to quantify <em>in vivo</em> Gd retention to investigate the potential toxicity of these agents. This study involves the optimization of the McMaster University <sup>238</sup>Pu/Be PGNAA facility for Gd measurements. Monte Carlo simulations were performed in parallel with the experimental work using MCNP version 5. Excellent agreement has been demonstrated between the Monte Carlo model of the system and the experimental measurements (both sensitivity and dosimetry). The initial study on the sensitivity of Gd demonstrated the feasibility of the measurement system. The Monte Carlo dosimetry simulations and experimental survey measurements demonstrated consistently that the radiation exposures for a single measurement were quite low, with an effective dose rate of 1.1 µSv/hr for a leg muscle measurement, 74 µSv/hr for a kidney measurement, and 48 µSv/hr for a liver measurement. The initial studies confirmed the Gd measurement feasibility which ultimately led to an <em>in vivo</em> pilot study on 10 healthy volunteers. The pilot study was successful with 9 out of 10 volunteers having measureable Gd in muscle above the <em>in vivo</em> detection limit of 0.58 ppm within 1 hour of administration, and the remaining participant had detectable Gd 196 minutes post administration. The concentrations measured ranged from 6.9 to 56 uncertainties different from zero. The system has been validated in humans and can now be used in future studies of short or long-term retention of Gd after contrast administration in at risk populations, such as those with reduced kidney function, patients with multiple exposures over the treatment period, and patients who are prescribed higher dosages. In addition, experiments and simulations were extended to another high neutron absorbing element, samarium (Sm).</p> / Doctor of Philosophy (PhD)

Identiferoai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/12342
Date10 1900
CreatorsGräfe, James L.
ContributorsMcNeill, Fiona E, Medical Physics
Source SetsMcMaster University
Detected LanguageEnglish
Typethesis

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