In the proposed research project, candidate TaO nanoparticle contrast agents for computed tomography (CT) will be developed with desired physical and biological properties for clinical use. We have developed a first-in-class zwitterioni tantalum oxide (TaO) nanoparticle CT contrast agent, specifically designed for contrast-enhanced CT imaging of large-to-obese patients. These nanoparticles have near-ideal physicochemical properties for clinical formulation and have shown equivalent biological performance (organ retention and acute tolerability) in rat dosing studies. We anticipate at least 50% radiation dose reduction when imaging this patient population, while producing image quality that is equivalent or better than what is provided with commercially-avail- able iodinated contrast agents.
Aim 1. Develop tantalum oxide nanoparticles that are safe and practical for eventual clinical use -Building upon our previous foundational research, we will develop new zwitterionic TaO nanoparticles by modifying particle size and shell chemistry to benefit CT imaging performance. We will demonstrate that the nanoparticles are biologically safe and have organ retention that is comparable to iodine-based counterparts.
Aim 2. Determine tantalum-specific CT imaging protocols to optimize image quality at reduced radiation dose for the large-to-obese patient population.-We will identify tantalum-specific CT acquisition protocols to provide equivalent or improved image quality (better signal-to-noise ratio, reduced artifacts) at 50% reduced radiation dose, when compared to iodine-based counterparts. We will perform computer simulations and phantom experiments using both simple and anatomically-relevant anthropomorphic phantoms, which represent a wide range of patient sizes.
Aim 3. Demonstrate improved imaging safety without loss of diagnostic performance in a porcine animal model that is representative of the large-to-obese patient population. -We will demonstrate contrast dose and/or radiation dose reduction (improved imaging safety) using a porcine animal model mimicking large-to-obese patients. We will characterize diagnostic performance, using metrics that are a function of the imaging signal-to-noise ratio.

Public Health Relevance

For CT imaging, contrast agents are critical to highlight vascular anatomy and pathology and to image end organs. However, currently available injectable agents (all iodine-based) have several limitations, including: iodine-related adverse effects; indistinguishability from calcified plaque or bone; rapid pharmacokinetics, leading to leakage into interstitial space; and high viscosity, limiting injection rate. We have developed new contrast agents based on TaO nanoparticles that will address these limitations to allow for expanded diagnostic applications as well as decrease the radiation dose to patients.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Nanotechnology Study Section (NANO)
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Conroy, Richard
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General Electric Global Research Center
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Lambert, Jack W; Sun, Yuxin; Ordovas, Karen G et al. (2018) Improved Calcium Scoring at Dual-Energy Computed Tomography Angiography Using a High-Z Contrast Element and Novel Material Separation Technique. J Comput Assist Tomogr 42:459-466
Euler, Andre; Solomon, Justin; FitzGerald, Paul F et al. (2018) Can Realistic Liver Tissue Surrogates Accurately Quantify the Impact of Reduced-kV Imaging on Attenuation and Contrast of Parenchyma and Lesions? Acad Radiol :
Lambert, Jack W; Sun, Yuxin; Stillson, Carol et al. (2018) An Intravascular Tantalum Oxide-based CT Contrast Agent: Preclinical Evaluation Emulating Overweight and Obese Patient Size. Radiology 289:103-110
Dotson, Brandan; Lambert, Jack W; Wang, Zhen J et al. (2017) Benefit of iodine density images to reduce out-of-field image artifacts at rapid kVp switching dual-energy CT. Abdom Radiol (NY) 42:735-741
FitzGerald, Paul F; Colborn, Robert E; Edic, Peter M et al. (2017) Liquid tissue surrogates for X-ray and CT phantom studies. Med Phys 44:6251-6260
Lambert, Jack W; Sun, Yuxin; Gould, Robert G et al. (2017) An Image-Domain Contrast Material Extraction Method for Dual-Energy Computed Tomography. Invest Radiol 52:245-254
Yeh, Benjamin M; FitzGerald, Paul F; Edic, Peter M et al. (2017) Opportunities for new CT contrast agents to maximize the diagnostic potential of emerging spectral CT technologies. Adv Drug Deliv Rev 113:201-222
Lambert, Jack W; FitzGerald, Paul F; Edic, Peter M et al. (2017) The Effect of Patient Diameter on the Dual-Energy Ratio of Selected Contrast-Producing Elements. J Comput Assist Tomogr 41:505-510
Winklhofer, Sebastian; Lambert, Jack W; Wang, Zhen Jane et al. (2016) Reduction of peristalsis-related gastrointestinal streak artifacts with dual-energy CT: a patient and phantom study. Abdom Radiol (NY) 41:1456-65
Wu, En-Haw; Kim, So Yeon; Wang, Z Jane et al. (2016) Appearance and Frequency of Gas Interface Artifacts Involving Small Bowel on Rapid-Voltage-Switching Dual-Energy CT Iodine-Density Images. AJR Am J Roentgenol 206:301-6

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