The aim of the study was to determine optimal measurement conditions for assessment of brain perfusion with the use of optical contrast agent and time-resolved diffuse reflectometry in the near-infrared wavelength range. The source-detector separation at which the distribution of time of flights (DTOF) of photons provided useful information on the inflow of the contrast agent to the intracerebral brain tissue compartments was determined. Series of Monte Carlo simulations was performed in which the inflow and washout of the dye in extra- and intracerebral tissue compartments was modeled and the DTOFs were obtained at different source-detector separations. Furthermore, tests on diffuse phantoms were carried out using a time-resolved setup allowing the measurement of DTOFs at 16 source-detector separations. Finally, the setup was applied in experiments carried out on the heads of adult volunteers during intravenous injection of indocyanine green. Analysis of statistical moments of the measured DTOFs showed that the source-detector separation of 6 cm is recommended for monitoring of inflow of optical contrast to the intracerebral brain tissue compartments with the use of continuous wave reflectometry, whereas the separation of 4 cm is enough when the higher-order moments of DTOFs are available.