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 SDϕ), single-slope intensity and phase (SSI and SSϕ), and dual-slope intensity and phase (DSI and DSϕ). 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_SDϕ 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 DSϕ for a thin extracerebral layer (L_ec < 13 mm), whereas it is greater for DSϕ than DSI for a thicker extracerebral layer.