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.

Dual-energy computed tomography using a gantry-based preclinical cone-beam microcomputed tomography scanner

“…The preparation of the Er-based ex vivo vascular perfusion contrast agent has been previously described by Tse et al. ; 22 briefly, perfusion of a sample required the formulation of a catalyzing curing agent and the Er-based suspension.…”

“…The Er-based contrast agent was comprised of a two-part silicone elastomer (Microfil 132, FlowTech Inc., Massachusetts, USA) with uniformly dispersed Er2O3 nanoparticles (nominal diameter 50 nm, Nanostructured and Amorphous Materials, Texas, USA). To create a volume of 30 mL, sufficient for a single rat hindlimb perfusion, 4.0 g of Er2O3 (13.3% w/v) was mixed within 8.73 mL of MV-132 and 17.47 mL of MV-diluent and probe sonicated for a total of 35 min 22 . The remaining 3.8 mL was comprised of the curing agent, as previously described, added prior to perfusion.…”

“…A DECT-compatible erbium (Er)-based ex vivo vascular perfusion contrast agent has been previously developed and characterized 22 . The Er-based suspension is ideally suited for DECT as its absorption K-edge (i.e., 57.5 keV) is located close to the mean energy of micro-CT scanners with a 90-kVp maximum tube potential.…”

Polymer Assembly Encapsulation of Lanthanide Nanoparticles as Contrast Agents for In Vivo Micro-CT

“…Erbium, which we have demonstrated to be an excellent contrast agent for ex vivo imaging, was selected as the lanthanide. 27 Oleate-coated NaErF 4 nanoparticles (ErNP) were synthesized and encapsulated into core-shell nanoassemblies via nanoprecipitation using a series of amphiphilic block copolymers ( Figure 1). A sequence of optimization steps was then performed to identify an ideal polymer, which encapsulates a high lanthanide content while remaining colloidally stable after redispersion in saline and a mouseblood mimic.…”

Corrigendum to “Erbium-Based Perfusion Contrast Agent for Small-Animal Microvessel Imaging”

“…In the article titled “Erbium-Based Perfusion Contrast Agent for Small-Animal Microvessel Imaging” [ 1 ], there were errors in the scale bars in Figure 3 , which should be corrected as follows:…”