Fluorescence imaging of tissues offer an essential means for studying biological systems. Autofluorescence becomes a serious issue in tissue imaging under excitation at UV-vis wavelengths where biological molecules compete with the fluorophore. To address this critical issue, a novel class of fluorophores that can :be excited at, similar to 900 nm under two-photon excitation conditions and emits in the red wavelength region (>= 600 nm) has been disclosed. The new pi-extended dipolar dye system, shows several advantageous features including minimal antofluorescence in tissue imaging and pronounced solvent-sensitive emission behavior, compared with a widely used two-photon absorbing dye, acedan. As an important application of the new dye system, one of the dyes was developed into a fluorescent probe for amyloicl-beta plaques, a key biomarker of Alzheimer's disease. The probe enabled in Vivo imaging of amyloid-beta plaques in a disease-model mouse, with negligible background signal. The new dye system has great potential for the development of other types of two-photon fluorescent probes and tags for imaging of tissues with minimal autofluorescence.