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.

Objective: Venous leg ulcers (VLUs) comprise 80% of leg ulcers. One of the key parameters that can promote healing of VLUs is tissue oxygenation. To date, clinicians have employed visual inspection of the wound site to determine the healing progression of a wound. Clinicians measure the wound size and check for epithelialization. Imaging for tissue oxygenation changes surrounding the wounds can objectively complement the subjective visual inspection approach. Herein, a handheld noncontact near-infrared optical scanner (NIROS) was developed to measure tissue oxygenation of VLUs during weeks of treatment. Approach: Continuous-wave-based diffuse reflectance measurements were processed using Modified Beer-Lambert's law to obtain changes in tissue oxygenation (in terms of oxy-, deoxy-, total hemoglobin, and oxygen saturation). The tissue oxygenation contrast obtained between the wound and surrounding tissue was longitudinally mapped across weeks of treatment of four VLUs (healing and nonhealing cases). Results: It was observed that wound to background tissue oxygenation contrasts in healing wounds diminished and/or stabilized, whereas in the nonhealing wounds it did not. In addition, in a very slow-healing wound, wound to background tissue oxygenation contrasts fluctuated and did not converge. Innovation: Near-infrared imaging of wounds to assess healing or nonhealing of VLUs from tissue oxygenation changes using a noncontact, handheld, and low-cost imager has been demonstrated for the first time. Conclusion:The tissue oxygenation changes in wound with respect to the surrounding tissue can provide an objective subclinical physiological assessment of VLUs during their treatment, along with the gold-standard visual clinical assessment.

Objective: Cerebral autoregulation limits the variability of cerebral blood flow (CBF) in the presence of systemic arterial blood pressure (ABP) changes. Monitoring cerebral autoregulation is important in the Neurocritical Care Unit (NCCU) to assess cerebral health. Here, our goal is to identify optimal frequency-domain near-infrared spectroscopy (FD-NIRS) parameters and apply a hemodynamic model of coherent hemodynamics spectroscopy (CHS) to assess cerebral autoregulation in healthy adult subjects and NCCU patients.Methods: In five healthy subjects and three NCCU patients, ABP oscillations at a frequency around 0.065 Hz were induced by cyclic inflation-deflation of pneumatic thigh cuffs. Transfer function analysis based on wavelet transform was performed to measure dynamic relationships between ABP and oscillations in oxy- (O), deoxy- (D), and total- (T) hemoglobin concentrations measured with different FD-NIRS methods. In healthy subjects, we also obtained the dynamic CBF-ABP relationship by using FD-NIRS measurements and the CHS model. In healthy subjects, an interval of hypercapnia was performed to induce cerebral autoregulation impairment. In NCCU patients, the optical measurements of autoregulation were linked to individual clinical diagnoses.Results: In healthy subjects, hypercapnia leads to a more negative phase difference of both O and D oscillations vs. ABP oscillations, which are consistent across different FD-NIRS methods and are highly correlated with a more negative phase difference CBF vs. ABP. In the NCCU, a less negative phase difference of D vs. ABP was observed in one patient as compared to two others, indicating a better autoregulation in that patient.Conclusions: Non-invasive optical measurements of induced phase difference between D and ABP show the strongest sensitivity to cerebral autoregulation. The results from healthy subjects also show that the CHS model, in combination with FD-NIRS, can be applied to measure the CBF-ABP dynamics for a better direct measurement of cerebral autoregulation.

We investigated the relationship between chromophore concentrations in two-layered scattering media and the apparent chromophore concentrations measured with broadband optical spectroscopy in conjunction with commonly used homogeneous medium inverse models. We used diffusion theory to generate optical data from a two-layered distribution of relevant tissue absorbers, namely, oxyhemoglobin, deoxyhemoglobin, water, and lipids, with a top-layer thickness in the range 1–15[Formula: see text]mm. The generated data consisted of broadband continuous-wave (CW) diffuse reflectance in the wavelength range 650–1024[Formula: see text]nm, and frequency-domain (FD) diffuse reflectance at 690 and 830[Formula: see text]nm; two source-detector distances of 25 and 35[Formula: see text]mm were used to simulate a dual-slope technique. The data were inverted using diffusion theory for a semi-infinite homogeneous medium to generate reduced scattering coefficients at 690 and 830[Formula: see text]nm (from FD data) and effective absorption spectra in the range 650–1024[Formula: see text]nm (from CW data). The absorption spectra were then converted into effective total concentration and oxygen saturation of hemoglobin, as well as water and lipid concentrations. For absolute values, it was found that the effective hemoglobin parameters are typically representative of the bottom layer, whereas water and lipid represent some average of the respective concentrations in the two layers. For concentration changes, lipid showed a significant cross-talk with other absorber concentrations, thus indicating that lipid dynamics obtained in these conditions may not be reliable. These systematic simulations of broadband spectroscopy of two-layered media provide guidance on how to interpret effective optical properties measured with similar instrumental setups under the assumption of medium homogeneity.