Most of the in vivo studies mentioned above have relied on a simple head model described as a homogeneous semi-infinite medium.1,6–10,16,19–22,25,26 This model has shown promising results in piglets and infants,5,8,9,11,20,22,27 but it is widely recognized that, in the case of the adult head, its oversimplification causes strong contamination of the brain optical properties by those of the extracerebral tissue. For the FDMD approach, Franceschini et al.12 have shown, with simulations and phantom measurements in a slab geometry, that when a superficial layer thicker than is present, the error on the retrieved absorption of the second layer can exceed 50%. We have previously investigated with simulated data the performance of the FDMD method on realistic head geometries at different ages.28 We showed that, while it provides accurate results in infants up to 1 year of age (10 to 15% error), its application to adult heads introduces large errors (20 to 45%). The FDMD method is therefore not directly translatable to adult head measurements. For a simple two-layer phantom geometry, Kienle et al. showed that using the TD analytical solution of the diffusion equation for a homogeneous medium induces strong contamination of the second layer optical properties by those of the first layer.17 Similarly, based on Monte Carlo simulations guided by in vivo measurements on the adult forehead, Comelli et al. showed that time-resolved data fitted with a homogeneous model return absorption and reduced scattering coefficients much closer to superficial layer values (scalp and skull) than to those of deeper layers (white and gray matter).16 This was further confirmed experimentally by Ohmae et al., who compared baseline absolute measurement of CBV obtained by positron emission tomography (PET) and by TD-NIRS.29 While the two modalities showed good correlation, the PET measures of CBV were 50% higher than those assessed by TD-NIRS, which in turn were more similar to the PET measure of scalp blood volume.