Recent advances in near-infrared spectroscopy (NIRS) allow measurements of absolute tissue oxygen saturation (TOI) using spatially resolved spectroscopy (SRS), while enabling better depth sensitivity. However concerns remain regarding the relative contribution of the extracranial circulation to the cerebral NIRS TOI signal. In this study we investigated this during a period of selective rise in cerebral blood flow (CBF) produced by the administration of acetazolamide (ACZ) in 10 healthy volunteers. A two channel spectrometer (NIRO 300, Hamamatsu Photonics KK) was used to measure absolute cerebral TOI over the frontal cortex using the SRS technique using an optode spacing of 5 cm and 1.5 cm for channel 1 and 2 respectively. After ACZ administration we were able to observe a significant increase in the velocity of middle cerebral artery (V(mca), measured with the transcranial Doppler (TCD)) which was accompanied by an increase in TOI as monitored by the NIRO 300 with an optode spacing of 5 cm but not with an optode spacing of 1.5 cm. Furthermore a direct relationship was seen between the V(mca) and the TOI measured at 5 cm optode spacing. This work suggests that using this commercial NIRS instrument with an optode spacing of 5 cm one is able to detect the intracranial changes.