Time-domain geometrical localization of point-like fluorescence inclusions in turbid media with early photon arrival times.

We introduce a novel approach for localizing a plurality of discrete point-like fluorescent inclusions embedded in a thick turbid medium using time-domain measurements. The approach uses early photon information contained in measured time-of-flight distributions originating from fluorescence emission. Fluorescence time point-spread functions (FTPSFs) are acquired with ultrafast time-correlated single photon counting after short pulse laser excitation. Early photon arrival times are extracted from the FTPSFs obtained from several source-detector positions. Each source-detector measurement allows defining a geometrical locus where an inclusion is to be found. These loci take the form of ovals in 2D or ovoids in 3D. From these loci a map can be built, with the maxima thereof corresponding to positions of inclusions. This geometrical approach is supported by Monte Carlo simulations performed for biological tissue-like media with embedded fluorescent inclusions. To validate the approach, several experiments are conducted with a homogeneous phantom mimicking tissue optical properties. In the experiments, inclusions filled with indocyanine green are embedded in the phantom and the fluorescence response to a short pulse of excitation laser is recorded. With our approach, several inclusions can be localized with low millimeter positional error. Our results support the approach as an accurate, efficient, and fast method for localizing fluorescent inclusions embedded in highly turbid media mimicking biological tissues. Further Monte Carlo simulations on a realistic mouse model show the feasibility of the technique for small animal imaging.