Use of nonlinear upconverting nanoparticles provides increased spatial resolution in fluorescence diffuse imaging

Fluorescence diffuse imaging (FDI) suffers from limited spatial resolution. In this Letter, we report a scanning imaging approach to increase the resolution of FDI using nonlinear fluorophores. The resolution of a linear fluorophore was compared with nonlinear upconverting nanoparticles (NaYF(4):Yb(3+)/Tm(3+)) in a tissue phantom. A resolution improvement of a factor of 1.3 was found experimentally. Simulations suggested a maximum resolution improvement of a factor of 1.45. Usage of nonlinear fluorophores is a promising method for increasing the spatial resolution in FDI.