Contrast agent imaging using an optimized table-top x-ray fluorescence and photon-counting computed tomography imaging system

dc.contributor.authorDunning, Chelsea Amanda Saffron
dc.contributor.supervisorBazalova-Carter, Magdalena of Physics and Astronomyen_US of Philosophy Ph.D.en_US
dc.description.abstractContrast agents are often crucial in medical imaging for disease diagnosis. Novel contrast agents, such as gold nanoparticles (AuNPs) and lanthanides, are being ex- plored for a variety of clinical applications. Preclinical testing of these contrast agents is necessary before being approved for use in humans, which requires the use of small animal imaging techniques. Small animal imaging demands the detection of these contrast agents in trace amounts at acceptable imaging time and radiation dose. Two such imaging techniques include x-ray fluorescence computed tomography (XFCT) and photon-counting CT (PCCT). XFCT combines the principles of CT with x-ray fluorescence by detecting fluorescent x-rays from contrast agents at various projections to reconstruct contrast agent maps. XFCT can image trace amounts of AuNPs but is limited to small animal imaging due to fluorescent x-ray attenuation and scatter. PCCT uses photon-counting detectors that separate the CT data into energy bins. This enables contrast agent detection by recognizing the energy dependence of x-ray attenuation in different materials, independent of AuNP depth, and can provide anatomical information that XFCT cannot. To achieve the best of both worlds, we modeled and built a table-top x-ray imaging system capable of simultaneous XFCT and PCCT imaging. We used Monte Carlo simulation software for the following work in XFCT imaging of AuNPs. We simulated XFCT induced by x-ray, electron, and proton beams scanning a small animal-sized object (phantom) containing AuNPs with Monte Carlo techniques. XFCT induced by x-rays resulted in the best image quality of AuNPs, however high-energy electron and medium-energy proton XFCT may be feasible for on-board x-ray fluorescence techniques during radiation therapy. We then simulated a scan of a phantom containing AuNPs on a table-top system to optimize the detector arrangement, size, and data acquisition strategy based on the resulting XFCT image quality and available detector equipment. To enable faster XFCT data acquisition, we separately simulated another AuNP phantom and determined the best collimator geometry for Au fluorescent x-ray detection. We also performed experiments on our table-top x-ray imaging system in the lab. Phantoms containing multiples of three lanthanide contrast agents were scanned on our tabletop x-ray imaging system using a photon-counting detector capable of sustaining high x-ray fluxes that enabled PCCT. We used a novel subtraction algorithm for reconstructing separate contrast agent maps; all lanthanides were distinct at low concentrations including gadolinium and holmium that are close in atomic number. Finally, we performed the first simultaneous XFCT and PCCT scan of a phantom and mice containing both gadolinium and gold based on the optimized parameters from our simulations. This dissertation outlines the development of our tabletop x-ray imaging system and the optimization of the complex parameters necessary to obtain XFCT and PCCT images of multiple contrast agents at biologically-relevant concentrations.en_US
dc.identifier.bibliographicCitationChelsea A. S. Dunning and Magdalena Bazalova-Carter. Sheet beam x-ray fluorescence computed tomography (XFCT) imaging of gold nanoparticles. Medical Physics, 45(6):2572–2582, 2018.en_US
dc.identifier.bibliographicCitationCAS Dunning and M Bazalova-Carter. Optimization of a table-top x-ray fluorescence computed tomography (XFCT) system. Physics in Medicine & Biology, 63(23):235013, 2018.en_US
dc.identifier.bibliographicCitationC. A. S. Dunning and M. Bazalova-Carter (2019). X-ray fluorescence computed tomography induced by photons, electrons, and protons. IEEE Transactions on Medical Imaging, 38 (12), 2735-2743.en_US
dc.identifier.bibliographicCitationC. A. S. Dunning, J. O’Connell, S. M. Robinson, K. J. Murphy, A. L. Frencken, F. C. J. M. van Veggel, K. Iniewski, and M. Bazalova-Carter (2020). Photon-counting computed tomography of lanthanide contrast agents with a high-flux 330 μm-pitch cadmium zinc telluride (CZT) detector on a table-top system. Journal of Medical Imaging, 7(3), 033502.en_US
dc.identifier.bibliographicCitationC. A. S. Dunning and M. Bazalova-Carter (2020). Design of a combined x-ray fluorescence computed tomography (CT) and photon-counting CT table-top imaging system. Journal of Instrumentation, 15 P06031.en_US
dc.rightsAvailable to the World Wide Weben_US
dc.subjectx-ray fluorescenceen_US
dc.subjectcomputed tomographyen_US
dc.subjectcontrast agenten_US
dc.subjectgold nanoparticlesen_US
dc.subjectimage reconstructionen_US
dc.subjectphoton counting detectorsen_US
dc.subjecttable-top imagingen_US
dc.subjectMonte Carlo simulationsen_US
dc.titleContrast agent imaging using an optimized table-top x-ray fluorescence and photon-counting computed tomography imaging systemen_US


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