A Spectral of Library Nanoparticle Contrast Agents for Spectral (Color) X-ray Imaging

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This award by the Biomaterials program in the Division of Materials Research to University of Notre Dame is to develop a spectral library of nanoparticle X-ray contrast agents for spectral (color) X-ray imaging. This award is cofunded by the Particulate and Multiphase Processes program in the Division of Chemical, Bioengineering, Environmental, and Transport Systems. Recent advances in energy-sensitive X-ray detectors have made spectral computed tomography (CT) feasible by unmixing the energy-dependent attenuation profile of different materials. The commercialization of this technology is expected to bring a new revolution to X-ray imaging. However, spectral differences in physiological fluids and soft tissues are sufficiently small that contrast agents are needed to take full advantage of spectral CT. Therefore, fundamental materials research is needed to design a spectral library of X-ray contrast agents in order to fully capitalize on the capabilities of spectral CT. The most appropriate combinations of contrast agents for spectral CT are not known and unavailable even for preclinical research. The core composition of the nanoparticles will be tailored to include materials with high atomic numbers encased in silica shells; these will be characterized with respect to known x-ray absorption spectra (K-, L-absorption edges) diagnostic for distinct core elements (Au, Bi, Ce, Gd and Hf). The nanoparticle shell will provide a common platform for surface functionalization with molecular ligands chosen to impart colloidal stability, cytocompatibility, and/or targeting. This design will lead to a common, but widely applicable, spectral library that is adaptable to different needs, such as passive vs. targeted delivery via control of the nanoparticle size and surface functionalization. Broader impacts of this project include: 1) providing research training and mentoring to undergraduate and high school students in the researchers laboratory; 2) incorporation of this research into instructional content on targeted nanoparticles as imaging and therapeutic agents, and 3) providing a new diagnostic tools for biomedicine.For the last century, X-ray imaging has been the primary means of non-invasive imaging enabling physicians to diagnose and treat disease and injury. Radiography was revolutionized in the 1970s by the advent of computed tomography (CT) which enabled three-dimensional imaging. Recent developments have made spectral (color) CT possible for the first time. This technology will lead to a new revolution in X-ray imaging, but suitable contrast agents are lacking to fully capitalize on the capabilities of spectral CT. The most appropriate combinations of contrast agents for spectral CT are not known and unavailable even for preclinical research. Therefore, fundamental materials research is needed to design a set of spectral library as X-ray contrast agents. Spectral CT, combined with a spectral library of nanoparticle X-ray contrast agents developed in this project, will have a significant impact in biomedicine. This transformational technology will enable scientists and physicians to differentiate various materials, tissues, and fluids, and this was not previously possible by X-ray imaging. Thus, the impact could be far-reaching, affecting any preclinical and clinical X-ray imaging for the study, diagnosis, and treatment of disease and injury. With resepect to outreach activities, this project will be providing research training to undergraduate students in collaboration with Notre Dame Center for Nano Science and Technology. Additionally, high school students will be trained in this reseach project to stimulate their interest in STEM topics. Integration of research and teaching will be accomplished by incorporating the research methods and results of this project into a lecture on targeted nanoparticles as imaging and therapeutic agents for an upper-level undergraduate and lower-level graduate course on Biomaterials.