Enhancing in vivo preclinical studies with VivoVist™ and photon-counting micro-CT imaging

Abstract

This study investigated the application of VivoVist™, a high-contrast micro-CT contrast agent, in spectral photoncounting (PC) micro-CT imaging in mouse models. With a long blood half-life, superior concentration, and reduced toxicity VivoVist, composed of barium (Ba)-based nanoparticles, offers a cost-effective solution for enhancing computed tomography (CT) imaging. To evaluate its efficacy, we employed an in-house developed spectral micro-CT with a photoncounting detector. VivoVist was administered through retro-orbital injection in a non-tumor-bearing C57BL/6 mouse and in two mice with MOC2 buccal tumors, with scans taken at various post-injection intervals. We used a multi-channel iterative reconstruction algorithm to provide multi-energy tomographic images with a voxel size of 125 microns or 75 microns for high-resolution scans; we performed post-reconstruction spectral decomposition with water, calcium (Ca), iodine (I), and barium (Ba) as bases. Our results revealed effective separation of Ba from I-based contrast agents with minimal cross-contamination and superior contrast enhancement for VivoVist at 39 keV. We also observed VivoVist's potential in delineating vasculature in the brain and its decreasing concentration in the blood over time post-injection, with increased uptake in the liver and spleen. We also explored the simultaneous use of VivoVist and liposomal iodinated nanoparticles in a cancer study involving radiation therapy. Our findings reveal that VivoVist, combined with radiation therapy, did not significantly increase liposomal iodine accumulation within head and neck squamous cell carcinoma tumors. In conclusion, our work confirms VivoVist's promising role in enhancing PCCT imaging and its potential in studying combination therapy, warranting further investigation into its applications in diagnostics and radiotherapy.