Design and characterization of a dead-time regime enhanced early photon projection imaging system

Scattering of visible and near-infrared light in biological tissue reduces spatial resolution for imaging of tissues thicker than 100 μm. In this study, an optical projection imaging system is presented and characterized that exploits the dead-time characteristics typical of photon counting modules based on single photon avalanche diodes (SPADs). With this system, it is possible to attenuate the detection of more scattered late-arriving photons, such that detection of less scattered early-arriving photons can be enhanced with increased light intensity, without being impeded by the maximum count rate of the SPADs. The system has the potential to provide transmittance-based anatomical information or fluorescence-based functional information (with slight modification in the instrumentation) of biological samples with improved resolution in the mesoscopic domain (0.1-2 cm). The system design, calibration, stability, and performance were evaluated using simulation and experimental phantom studies. The proposed system allows for the detection of very-rare early-photons at a higher frequency and with a better signal-to-noise ratio. The experimental results demonstrated over a 3.4-fold improvement in the spatial resolution using early photon detection vs. conventional detection, and a 1000-fold improvement in imaging time using enhanced early detection vs. conventional early photon detection in a 4-mm thick phantom with a tissue-equivalent absorption coefficient of μ_a = 0.05 mm^-1 and a reduced scattering coefficient of μ_s' = 5 mm^-1.