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The use of hybrid PMT with reduced afterpulsing allows acquisition of TD fNIRS signals over a larger dynamic and temporal range. Further, the space-multiplexing approach implemented by means of a cascade of fast fiber optic switches that sequentially delivers the different wavelengths in different injection channels, eliminates the cross-talk between TD NIRS signal at different wavelengths (Contini et al., 2013b). The research group at Physikalisch-Technische Bundesanstalt, Berlin, Germany has been testing novel approaches for light delivery and collection. A cascade of splitters is used to illuminate in parallel several injection points to potentially reduce power loss. Time-multiplexing of TD NIRS signal from different channels allows parallel detections. Moreover, advanced PMT with improved sensitivity in the NIR (e.g. GaAs surface) or reduced after-pulsing (e.g. hybrid PMT) has been tested (Steinkellner S1PR1 et al., 2012). In a different set-up, a novel non-contact system is used that utilizes a quasi-null source detector separation approach for TD NIRS, taking advantage of polarization-sensitive detection and a state-of-the-art fast-gated SPAD to detect late photons PLK inhibitor only, bearing information about deeper layers of the biological tissue. Measurements on phantoms and preliminary in vivo tests demonstrate the feasibility of the non-contact approach for the detection of optically absorbing perturbations buried up to a few centimeters beneath the surface of a tissue-like turbid medium (Mazurenka et al., 2012?and?Mazurenka et al., 2013). On the basis of the experience gained with advanced laboratory setups (Pifferi et al., 2008?and?Tosi et al., 2011), a next generation TD fNIRS prototype implementing the null distance approach has been recently designed and developed at Politecnico di Milano, Milan, Italy. The instrument is based on a custom developed SC fiber laser (Fianium Ltd., Southampton, United Kingdom), Bleomycin providing two independent outputs at 710?nm and 820?nm, with a repetition frequency of 40?MHz, 100?mW average power at each wavelength, and a FWHM of