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

用于光谱（彩色）X 射线成像的纳米粒子对比剂库的光谱

• 批准号: 1309587
• 负责人: Ryan Roeder
• 金额: $ 38万
• 依托单位: University of Notre Dame
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1309587&HistoricalAwards=false
• 关键词: Spectral; Library; Nanoparticle; Contrast; Agents

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.

该奖项由Notre Dame大学材料研究部的生物材料项目授予，旨在开发用于光谱（彩色）X射线成像的纳米颗粒X射线造影剂光谱库。该奖项由化学，生物工程，环境和运输系统部门的颗粒和多相过程计划共同资助。能量敏感的X射线探测器的最新进展已经使得光谱计算机断层扫描（CT）通过分解不同材料的能量依赖的衰减轮廓而变得可行。 该技术的商业化有望为X射线成像带来新的革命。 然而，生理液体和软组织中的光谱差异足够小，因此需要造影剂来充分利用光谱CT。 因此，需要进行基础材料研究来设计X射线造影剂的光谱库，以便充分利用光谱CT的能力。 用于光谱CT的最合适的造影剂组合是未知的，甚至对于临床前研究也是不可用的。 纳米颗粒的核组成将被定制为包括被包裹在二氧化硅壳中的具有高原子序数的材料;这些将相对于已知的X射线吸收光谱（K-、L-吸收边缘）来表征，所述X射线吸收光谱诊断不同的核元素（Au、Bi、Ce、Gd和Hf）。 纳米颗粒壳将提供用于表面官能化的共同平台，所述表面官能化具有被选择以赋予胶体稳定性、细胞相容性和/或靶向的分子配体。 这种设计将产生一种通用但广泛适用的光谱库，该光谱库可适应不同的需求，例如通过控制纳米颗粒尺寸和表面功能化的被动与靶向递送。 该项目更广泛的影响包括：1）在研究人员实验室为本科生和高中生提供研究培训和指导; 2）将该研究结合到关于靶向纳米颗粒作为成像和治疗剂的教学内容中，以及3）为生物医学提供新的诊断工具。在上个世纪，X射线成像是非侵入性成像的主要手段，使医生能够诊断和治疗疾病和损伤。 20世纪70年代，计算机断层扫描（CT）的出现使放射摄影术发生了革命性的变化，它可以进行三维成像。 最近的发展使光谱（彩色）CT首次成为可能。 这项技术将导致X射线成像的新革命，但缺乏合适的造影剂来充分利用光谱CT的能力。 用于光谱CT的最合适的造影剂组合是未知的，甚至对于临床前研究也是不可用的。 因此，需要进行基础材料研究，设计一套光谱库作为X射线造影剂。 光谱CT与该项目中开发的纳米颗粒X射线造影剂光谱库相结合，将对生物医学产生重大影响。 这种变革性的技术将使科学家和医生能够区分各种材料、组织和液体，而这在以前是X射线成像无法实现的。 因此，影响可能是深远的，影响任何临床前和临床X射线成像的研究，诊断和治疗疾病和损伤。与respect到外展活动，该项目将提供研究培训，本科生与圣母大学纳米科学与技术中心合作。此外，高中生将在这个研究项目中接受培训，以激发他们对STEM主题的兴趣。研究和教学的整合将通过将本项目的研究方法和结果纳入关于靶向纳米颗粒作为成像和治疗剂的讲座中来完成，用于生物材料的高级本科和低级研究生课程。