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Light is a powerful non-invasive tool that can be exploited to probe highly scattering media like biological tissues for different purposes, from the detection of brain activity to the characterization of cancer lesions. In the last decade, timedomain diffuse optics (TDDO) systems demonstrated improved sensitivity when using time-gated acquisition chains and short source-detector separations (ρ), both theoretically and experimentally. However, the sensitivity to localized absorption changes buried inside a diffusive medium strongly depends on many parameters such as: SDS, laser power, delay and width of the gating window, absorption and scattering properties of the medium, instrument response function (IRF) shape, etc. In particular, relevant effects due to slow tails in the IRF were noticed, with detrimental effects on performances. We present simulated experimental results based on the diffusion approximation of the Radiative Transfer Equation and the perturbation theory subjected to the Born approximation. To quantify the system sensitivity to deep (few cm) and localized absorption perturbations, we exploited contrast and contrast-to-noise ratio (CNR), which are internationally agreed on standardized figures of merit. The purpose of this study is to determine which parameters have the greatest impact on these figures of merit, thus also providing a range of best operative conditions. The study is composed by two main stages: the former is a comparison between simulations and measurements on tissue-mimicking phantom, while the latter is a broad simulation study in which all relevant parameters are tuned to determine optimal measurement conditions. This study essentially demonstrates that under the influence of the slow tails in the IRF, the use of a small SDS no longer corresponds to optimal contrast and CNR. This work sets the ground for future studies with next-generation of TDDO components, presently under development, providing useful hints on relevant features to which one should take care when designing TDDO components.
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