Single-distance and dual-slope frequency-domain near-infrared spectroscopy to assess skeletal muscle hemodynamics.

Significance: Non-invasive optical measurements of deep tissue (e.g., muscle) need to take into account confounding contributions from baseline and dynamic optical properties of superficial tissue (adipose tissue). Aim: Discriminate superficial and deep tissue hemodynamics using data collected with frequency-domain (FD) near-infrared spectroscopy (NIRS) in a dual-slope (DS) configuration. Approach: Experimental data were collected in vivo on the forearm of three human subjects during a 3-min arterial occlusion or 1-min venous occlusion. Theoretical data were generated using diffusion theory for two-layered media with varying values of the reduced scattering coefficient (µs') (range: 0.5 to 1.1 mm-1) and absorption coefficient (µa) (range: 0.005-0.015 mm-1) of the two layers, and top layer thickness (range: 2 to 8 mm). Data were analyzed using diffusion theory for a homogeneous semi-infinite medium. Results: Experimental data in vivo were consistent with simulated data for a two-layered medium with a larger µs' in the top layer, comparable absorption changes in the top and bottom layers during venous occlusion, and smaller absorption changes in the top vs. bottom layers during arterial occlusion. Conclusions: The dataset generated by DS FD-NIRS may allow for discrimination of superficial and deep absorption changes in two-layered media, thus lending itself to individual measurements of hemodynamics in adipose and muscle tissue.

Estimating Systemic Cognitive States from a Mixture of Physiological and Brain Signals.

As human-machine teams are being considered for a variety of mixed-initiative tasks, detecting and being responsive to human cognitive states, in particular systematic cognitive states, is among the most critical capabilities for artificial systems to ensure smooth interactions with humans and high overall team performance. Various human physiological parameters, such as heart rate, respiration rate, blood pressure, and skin conductance, as well as brain activity inferred from functional near-infrared spectroscopy or electroencephalogram, have been linked to different systemic cognitive states, such as workload, distraction, or mind-wandering among others. Whether these multimodal signals are indeed sufficient to isolate such cognitive states across individuals performing tasks or whether additional contextual information (e.g., about the task state or the task environment) is required for making appropriate inferences remains an important open problem. In this paper, we introduce an experimental and machine learning framework for investigating these questions and focus specifically on using physiological and neurophysiological measurements to learn classifiers associated with systemic cognitive states like cognitive load, distraction, sense of urgency, mind wandering, and interference. Specifically, we describe a multitasking interactive experimental setting used to obtain a comprehensive multimodal data set which provided the foundation for a first evaluation of various standard state-of-the-art machine learning techniques with respect to their effectiveness in inferring systemic cognitive states. While the classification success of these standard methods based on just the physiological and neurophysiological signals across subjects was modest, which is to be expected given the complexity of the classification problem and the possibility that higher accuracy rates might not in general be achievable, the results nevertheless can serve as a baseline for evaluating future efforts to improve classification, especially methods that take contextual aspects such as task and environmental states into account.

Dual-slope imaging of cerebral hemodynamics with frequency-domain near-infrared spectroscopy.

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.

Broadband diffuse optical spectroscopy of two-layered scattering media containing oxyhemoglobin, deoxyhemoglobin, water, and lipids.

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 togenerate 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 mm. The generated data consisted of broadband continuous-wave (CW) diffuse reflectance in the wavelength range 650-1024 nm, and frequency-domain (FD) diffuse reflectance at 690 and 830 nm; two source-detector distances of 25 and 35 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 nm (from FD data) and effective absorption spectra in the range 650-1024 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.

Noninvasive Optical Measurements of Dynamic Cerebral Autoregulation by Inducing Oscillatory Cerebral Hemodynamics.

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.

Broadband absorption spectroscopy of heterogeneous biological tissue.

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.

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, 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.

Dual-Slope Diffuse Reflectance Instrument for Calibration-Free Broadband Spectroscopy.

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 (R 2 = 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.

Phase dual-slopes in frequency-domain near-infrared spectroscopy for enhanced sensitivity to brain tissue: First applications to human subjects.

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.

Tissue Oxygenation Changes to Assess Healing in Venous Leg Ulcers Using Near-Infrared Optical Imaging.

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.