Sensitivity of frequency-domain optical measurements to brain hemodynamics: simulations and human study of cerebral blood flow during hypercapnia

This study characterizes the sensitivity of noninvasive measurements of cerebral blood flow (CBF) by using frequency-domain near-infrared spectroscopy (FD-NIRS) and coherent hemodynamics spectroscopy (CHS). We considered six FD-NIRS methods: single-distance intensity and phase (SDI and SD ϕ ), single-slope intensity and phase (SSI and SS ϕ ), and dual-slope intensity and phase (DSI and DS ϕ ). Cerebrovascular reactivity (CVR) was obtained from the relative change in measured CBF during a step hypercapnic challenge. Greater measured values of CVR are assigned to a greater sensitivity to cerebral hemodynamics. In a first experiment with eight subjects, CVR SD ϕ was greater than CVR SDI ( p  < 0.01), whereas CVR DSI and CVR DSϕ showed no significant difference ( p  > 0.5). In a second experiment with four subjects, a 5 mm scattering layer was added between the optical probe and the scalp tissue to increase the extracerebral layer thickness ( L ec ), which caused CVR DSϕ to become significantly greater than CVR DSI ( p  < 0.05). CVR SS measurements yielded similar results as CVR DS measurements but with a greater variability, possibly resulting from instrumental artifacts in SS measurements. Theoretical simulations with two-layered media confirmed that, if the top (extracerebral) layer is more scattering than the bottom (brain) layer, the relative values of CVR DSI and CVR DSϕ depend on L ec . Specifically, the sensitivity to the brain is greater for DSI than DS ϕ for a thin extracerebral layer ( L ec < 13 mm), whereas it is greater for DS ϕ than DSI for a thicker extracerebral layer.