Erbium-Based Perfusion Contrast Agent for Small-Animal Microvessel Imaging

Abstract

Micro-computed tomography (micro-CT) facilitates the visualization and quantification of contrast-enhanced microvessels within intact tissue specimens, but conventional preclinical vascular contrast agents may be inadequate near dense tissue (such as bone). Typical lead-based contrast agents do not exhibit optimal X-ray absorption properties when used with X-ray tube potentials below 90 kilo-electron volts (keV). We have developed a high-atomic number lanthanide (erbium) contrast agent, with a K-edge at 57.5 keV. This approach optimizes X-ray absorption in the output spectral band of conventional microfocal spot X-ray tubes. Erbium oxide nanoparticles (nominal diameter < 50 nm) suspended in a two-part silicone elastomer produce a perfusable fluid with viscosity of 19.2 mPa-s. Ultrasonic cavitation was used to reduce aggregate sizes to <70 nm. Postmortem intact mice were perfused to investigate the efficacy of contrast agent. The observed vessel contrast was >4000 Hounsfield units, and perfusion of vessels < 10 μm in diameter was demonstrated in kidney glomeruli. The described new contrast agent facilitated the visualization and quantification of vessel density and microarchitecture, even adjacent to dense bone. Erbium’s K-edge makes this contrast agent ideally suited for both single- and dual-energy micro-CT, expanding potential preclinical research applications in models of musculoskeletal, oncological, cardiovascular, and neurovascular diseases.