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Objectives: in vitro assessment of the reproducibility and the optimal separation and position of the optodes in continuous wave (CW-) NIRS measurement of local inhomogeneities in absorption and/or scattering. Methods: a CW- NIRS system (OXYMON) was used with laser diodes at wavelengths of 767 nm, 845 nm, 905 nm, 945 nm and 975 nm. For practical considerations (dimensions of neonatal head) the measurements were performed on a cylindrical tissue-equivalent phantom (70 mm diameter of base material with µa = 0.01 mm-1 (800 nm) and µ's = 1.00 mm-1 (800 nm)), containing rods with 10 × absorption, or 10 × scattering, and 5 × both Monte Carlo simulations were carried out of a cylinder with transport scattering coefficient µ'e = 0.525 mm-1 and absorption coefficient µa = 0.075 mm-1 and two optode positions. Results: reproducibility of repeated measurements (n = 10) was ± 0.005 OD. Maximum OD in case of absorbing rod, and of absorbing + scattering rod was measured with optodes separated by 90° and rod position angle symmetrically (45°) in between. Minimum OD for these rods was obtained with optodes at 150° angle and rod position at 240° (i.e. relative to transmitting optode position at 0°). A second maximum OD was obtained at an optode angle 180° and rod position at 180°. Maximum OD (i.e. attenuation) for the scattering rod was at optode separation angle of 90° and rod at 0°. Minimum OD for this case was obtained with optode angle of 180° and rod positions around 80° and 280°. Maximum OD changes by absorbing rod were in the order of + 0.12 OD and -0.04 OD, respectively. Simulations at an optode separation angle of 90° showed a spatial sensitivity path enclosing the rod position at maximum absorption found experimentally. Conclusions: when considering the phantom as a realistic geometrical model for the neonatal head, it can be concluded that the optode position at 90° angle would be optimal for detecting an inhomogeneity at 15 mm depth, i.e. the location of the periventricular white matter. Since the rods are relatively strongly different from the base material the question remains to be answered whether local ischemia, which might lead to irreversible brain damage, can be detected by CW-NIRS.