Rare-earth doped particles as dual-modality contrast agent for minimally-invasive luminescence and dual-wavelength photoacoustic imaging

Multi-modal imaging is an emerging area that integrates multiple imaging modalities to simultaneously capture visual information over many spatial scales. Complementary contrast agents need to be co-developed in order to achieve high resolution and contrast. In this work, we demonstrated that rare-earth doped particles (REDPs) can be employed as dual-modal imaging agents for both luminescence and photoacoustic (PA) imaging to achieve intrinsic high contrast, temporal and spatial resolution, reaching deeper depth. REDPs synthesized with different surfactants (citric acid, polyacrylic acid, ethylenediaminetetraacetic acid and sodium citrate) exhibit tunable emission properties and PA signal amplitudes. Amongst these samples, sodium citrate-modified REDPs showed the strongest PA signals. Furthermore, since REDPs have multiple absorption peaks, they offer a unique opportunity for multi-wavelength PA imaging (e.g. PA signals were measured using 520 and 975 nm excitations). The in vivo PA images around the cortical superior sagittal sinus (SSS) blood vessel captured with enhanced signal arising from REDPs demonstrated that in addition to be excellent luminescent probes, REDPs can also be used as successful PA contrast agents. Anisotropic polyacrylic acid-modified REDPs were found to be the best candidates for dual-modal luminescence and PA imaging due to their strong luminescence and PA signal intensities.