Design and Synthesis of Nanoparticle Contrast Agents for Spectral (color) X-Ray Imaging

Abstract

Computed tomography (CT) is an important tool in clinical diagnostic imaging enabling three-dimensional anatomic imaging at high spatial resolution with short scan times. However, X-ray attenuation differences in physiological fluids and soft tissues are relatively small, requiring the use of contrast agents to achieve sufficient imaging contrast. Recent advances in energy-sensitive X-ray detectors have made spectral (color) CT commercially feasible by unmixing the energy-dependent attenuation profile of different materials and will potentially enable molecular imaging in CT. In order to leverage these capabilities for diagnostic imaging, we are developing a spectral library of nanoparticle contrast agents with K-shell absorption edges spaced at least 10 keV apart. The objective of this study was to demonstrate the ability of spectral CT to simultaneously detect up to three different contrast agents and unmixed their signals to create color images. Gadolinium oxide (Gd), hafnium oxide (Hf) and gold (Au) were chosen due to exhibiting K-edges spaced 10–20 keV apart. Core-shell nanoparticles of each composition were synthesized by various methods to have a core diameter of 15–20 nm and were coated with a silica shell at least 2–4 nm in thickness to create a common platform for surface functionalization. The contrast agents were imaged in a soft tissue equivalent phantom using source-side method for spectral CT imaging. The source-side approach utilized monochromatic synchrotron radiation at the Argonne National Laboratory which, while not clinically applicable, served as a gold standard due to providing the highest spectral resolution. The nanoparticles designed for this study have broad applications in biomedical imaging due to their modular assembly, potential for enabling multi-modal detection, and surface functionalization with biomolecules (e.g., antibodies, peptides or enzymes) for active targeting.