TOF-PET detector systems, and methods for imaging photon-emitting samples using the detector systems, are provided. The TOF-PET detector systems use large-area photodetectors with extremely high time-resolution and an approach to data collection and analysis that allows for the use of inexpensive low-density scintillator materials. The TOF-PET detector systems are characterized by their ability to identify, on a statistical basis, the transverse and depth location of the first of the series of energy deposition events that are generated when a gamma photon enters the low-density scintillator material.