Early-photon fluorescence tomography: spatial resolution improvements and noise stability considerations

In vivo tissue imaging using near-infrared light suffers from low spatial resolution and poor contrast recovery because of highly scattered photon transport. For diffuse optical tomography (DOT) and fluorescence molecular tomography (FMT), the resolution is limited to about 5-10% of the diameter of the tissue being imaged, which puts it in the range of performance seen in nuclear medicine. This paper introduces the mathematical formalism explaining why the resolution of FMT can be significantly improved when using instruments acquiring fast time-domain optical signals. This is achieved through singular-value analysis of the time-gated inverse problem based on weakly diffused photons. Simulations relevant to mouse imaging are presented showing that, in stark contrast to steady-state imaging, early time-gated intensities (within 200 ps or 400 ps) can in principle be used to resolve small fluorescent targets (radii from 1.5 to 2.5 mm) separated by less than 1.5 mm.