High-resolution fluorescence diffuse optical tomography developed with nonlinear upconverting nanoparticles.

Fluorescence diffuse optical tomography (FDOT) is an emerging biomedical imaging technique that can be used to localize and quantify deeply situated fluorescent molecules within tissues. However, the potential of this technique is currently limited by its poor spatial resolution. In this work, we demonstrate that the current resolution limit of FDOT can be breached by exploiting the nonlinear power-dependent optical emission property of upconverting nanoparticles doped with rare-earth elements. The rare-earth-doped core-shell nanoparticles, NaYF(4):Yb(3+)/Tm(3+)@NaYF(4) of hexagonal phase, are synthesized through a stoichiometric method, and optical characterization shows that the upconverting emission of the nanoparticles in tissues depends quadratically on the power of excitation. In addition, quantum-yield measurements of the emission from the synthesized nanoparticles are performed over a large range of excitation intensities, for both core and core-shell particles. The measurements show that the quantum yield of the 800 nm emission band of core-shell upconverting nanoparticles is 3.5% under an excitation intensity of 78 W/cm(2). The FDOT reconstruction experiments are carried out in a controlled environment using liquid tissue phantoms. The experiments show that the spatial resolution of the FDOT reconstruction images can be significantly improved by the use of the synthesized upconverting nanoparticles and break the current spatial resolution limits of FDOT images obtained from using conventional linear fluorophores as contrast agents.