We present a first in vivo application of phase dual‐slopes (DSϕ), measured with frequency‐domain near‐infrared spectroscopy on four healthy human subjects, to demonstrate their enhanced sensitivity to cerebral hemodynamics. During arterial blood pressure oscillations elicited at a frequency of 0.1 Hz, we compare three different ways to analyze either intensity (I) or phase (ϕ) data collected on the subject's forehead at multiple source‐detector distances: Single‐distance, single‐slope and DS. Theoretical calculations based on diffusion theory show that the method with the deepest maximal sensitivity (at about 11 mm) is DSϕ. The in vivo results indicate a qualitative difference of phase data (especially DSϕ) and intensity data (especially single‐distance intensity [SDI]), which we assign to stronger contributions from scalp hemodynamics to SDI and from cortical hemodynamics to DSϕ. Our findings suggest that scalp hemodynamic oscillations may be dominated by blood volume dynamics, whereas cortical hemodynamics may be dominated by blood flow velocity dynamics.

This work presents the design and validation of an instrument for dual-slope broadband diffuse reflectance spectroscopy. This instrument affords calibration-free, continuous-wave measurements of broadband absorbance of optically diffusive media, which may be translated into absolute absorption spectra by adding frequency-domain measurements of scattering at two wavelengths. An experiment on a strongly scattering liquid phantom (milk, water, dyes) confirms the instrument’s ability to correctly identify spectral features and measure absolute absorption. This is done by sequentially adding three dyes, each featuring a distinct spectral absorption, to the milk/water phantom. After each dye addition, the absorption spectrum is measured, and it is found to reproduce the spectral features of the added dye. Additionally, the absorption spectrum is compared to the absorption values measured with a commercial frequency-domain instrument at two wavelengths. The measured absorption of the milk/water phantom quantitatively agrees with the known water absorption spectrum (R2=0.98), and the measured absorption of the milk/water/dyes phantom quantitatively agrees with the absorption measured with the frequency-domain instrument in six of eight cases. Additionally, the measured absorption spectrum correctly recovers the concentration of one dye, black India ink, for which we could accurately determine the extinction spectrum (i.e., the specific absorption per unit concentration). The instrumental methods presented in this work can find applications in quantitative spectroscopy of optically diffusive media, and particularly in near-infrared spectroscopy of biological tissue.

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, CVRSDϕ was greater than CVRSDI (p < 0.01), whereas CVRDSI and CVRDSϕ 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 CVRDSϕ to become significantly greater than CVRDSI (p < 0.05). CVRSS measurements yielded similar results as CVRDS 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 CVRDSI and CVRDSϕ 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.

. Significance This work targets the contamination of optical signals by superficial hemodynamics, which is one of the chief hurdles in non-invasive optical measurements of the human brain. Aim To identify optimal source–detector distances for dual-slope (DS) measurements in frequency-domain (FD) near-infrared spectroscopy (NIRS) and demonstrate preferential sensitivity of DS imaging to deeper tissue (brain) versus superficial tissue (scalp). Approach Theoretical studies ( in-silico ) based on diffusion theory in two-layered and in homogeneous scattering media. In-vivo demonstrations of DS imaging of the human brain during visual stimulation and during systemic blood pressure oscillations. Results The mean distance (between the two source–detector distances needed for DS) is the key factor for depth sensitivity. In-vivo imaging of the human occipital lobe with FD NIRS and a mean distance of 31 mm indicated: (1) greater hemodynamic response to visual stimulation from FD phase versus intensity, and from DS versus single-distance (SD); (2) hemodynamics from FD phase and DS mainly driven by blood flow, and hemodynamics from SD intensity mainly driven by blood volume. Conclusions DS imaging with FD NIRS may suppress confounding contributions from superficial hemodynamics without relying on data at short source–detector distances. This capability can have significant implications for non-invasive optical measurements of the human brain.

Absorption spectra ( ∼ 600 to 1064 nm) of six tissues in three healthy volunteers were measured by combining dual-slope continuous-wave broadband spectroscopy with self-calibrated frequency-domain measurements of scattering at two wavelengths (690 and 830 nm). The spectral fit with a linear combination of oxy- and deoxyhemoglobin, water, and lipids extinction spectra is improved by a wavelength-independent absorption background. The need to introduce this background is assigned to the inhomogeneous distribution of absorbers in tissue. By using a two-layer model, the relationship between recovered concentrations and their two-layer values was investigated, and the implications for non-invasive tissue spectroscopy are discussed.