While near-infrared spectroscopy has been shown to be a useful technique for the non-invasive monitoring of cerebral hemodynamics, sensitivity to superficial hemodynamic changes continues to be a challenge in the field. Here, we apply a previously designed hexagonal dual-slope module to human subjects during a visual stimulation protocol. The enrolled subjects have different scalp-to-cortex distances, as measured with ultrasound imaging. This work investigates the cerebral hemodynamic response to visual stimulation as measured non-invasively by optical intensity (I) collected with a single distance (SD) or dual-slope (DS) source-detector arrangement [SDI(25 mm), SDI(35 mm), DSI]. The observed results in relation to scalp-to-cortex distance are then validated through theoretical simulations in two-layered media, and these simulations confirm that as the cortical depth increases the sensitivity to the brain decreases faster for single-distance measurements than dual-slope measurements. This finding supports the value of dual-slope measurements for enhanced sensitivity to the brain.
We used frequency-domain (FD) near-infrared spectroscopy (NIRS) in a dual-slope (DS) configuration to non-invasively assess skeletal muscle hemodynamics in the human forearm muscle. Our objective is to leverage FD-NIRS data (intensity and phase) collected in DS mode (a combination of single-distance and multi-distance measurements) to differentiate superficial and deep tissue hemodynamics. FD-NIRS signals feature contributions from adipose tissue (AT), muscle tissue (MT), and possibly bone tissue, in cases of relatively thin AT and MT layers. We performed measurements of blood flow (BF) and oxygen consumption (OC) using venous occlusion and arterial occlusion protocols, respectively. Additionally, we performed theoretical simulations based on diffusion theory to guide the interpretation of our experimental results. First, we were able to show that our experimental results are consistent with a top layer (adipose tissue) that is more scattering than a bottom layer (muscle) and that absorption changes are greater in the top layer during venous occlusion whereas they are greater in the bottom layer during arterial occlusion, in agreement with previous results on different human subjects [C. Fernandez et al., J. Biomed. Opt. 28, 125004 (2023)]. Second, we started measurements on subjects featuring a range of thicknesses of adipose and muscle tissue to explore the feasibility of discriminating superficial and deeper hemodynamics using the full information content of the data collected with DS FD-NIRS.
SignificanceNon-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).AimDiscriminate superficial and deep tissue hemodynamics using data collected with frequency-domain (FD) near-infrared spectroscopy (NIRS) in a dual-slope (DS) configuration.ApproachExperimental 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.ResultsExperimental 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.ConclusionsThe 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.
Functional Near-InfraRed Spectroscopy (NIRS) (fNIRS) is a powerful method for non-invasively measuring cerebral hemodynamics on human subjects. Measurement contamination from superficial tissue which do not represent the brain continues to be an issue. We have proposed the Dual-Slope (DS) approach which is less sensitive to superficial tissue compared to typical Single-Distance (SD) methods. This DS method has been applied to Diffuse Optical Imaging (DOI), designing and constructing a large source-detector array. Previous results suggested that DS phase (Φ) has intrinsically higher sensitivity to the brain compared to SD Intensity (I). To further investigate this finding, on a large population of subjects, a modular DS array is designed. Allowing for collection from different cortical locations during various protocols. These source-detector modules are hexagonal and contain 4 intra-module DS sets. Tessellation greatly expands the number of measurement sets through the creation of inter-module DS sets. In one example, we found a tessellation of 7 modules which generated 94 DS sets. The modules will be used to enable large population DS DOI studies. Here we present one example trace during a 3-back protocol. Examination of the DS traces suggest the expected higher DS Φ sensitivity to cerebral hemodynamics. Further, close observation of the results demonstrate the importance of considering both the Oxy-hemoglobin concentration change (ΔO) and Deoxy-hemoglobin concentration change (ΔD) during such protocols. The results indicated that if one observed only ΔO they would have mis-identified brain activation in the short SD I measurement. Other data-types and ΔD dynamics suggested that the short SD I was dominated by superficial blood-volume instead of the blood-flow dynamics associated with brain activation.
Cerebral hemodynamics, measured with near-infrared spectroscopy, that are coherent with changes in blood pressure can be analyzed with Coherent Hemodynamics Spectroscopy (CHS). Performing diffuse optical imaging during a CHS protocol provides the ability to spatially map cerebral hemodynamics and elucidate their relation to blood flow and blood volume dynamics. Here, we apply frequency-domain dual-slope optical imaging during a CHS protocol to demonstrate the preferential sensitivity to cerebral hemodynamics of dual-slope frequency-domain measurements as compared to traditional single-distance intensity measurements. Specifically, the results show that dual-slope phase measurements recorded hemodynamics that are mostly associated with blood-flow oscillations (as expected in the brain), while single distance intensity measurements recorded hemodynamics that are mostly associated with blood-volume oscillations (as expected in the scalp). Reconstructed dual-slope phase images showed the effect of a spatially variable skull thickness, which can cause heterogeneity within the reconstructed images. Future work will include measurements on multiple subjects and across multiple oscillation frequencies to further investigate the spatial distribution and frequency dependence of cerebral hemodynamic oscillations.
Measurements of absolute optical properties of scattering samples is valuable in the field of bio-medicine and beyond. However, achieving these measurements is complicated by the need for calibration and by the large sample volumes typically needed to meet common diffusion theory models. We propose a method for calibration free absolute measurements of the absorption coefficient (µa) and reduced scattering coefficient (µ 0 s ) in a relatively small volume (the size of a standard cuvette; 45 mm × 10 mm × 10 mm). This method utilizes the previously proposed Self-Calibrating (SC) / Dual-Slope (DS) geometry by placing two light sources on one face of the cuvette and two optical detectors on the opposite face. This leads to the proposal of the Dual-Ratio of the complex Transmittance (Te) (DR{Te}), a method with the same advantages as SC / DS but with less geometric requirements and constraints. Here we confirm that measurement of DR{Te} from a cuvette may be converted to absolute optical properties. We then investigate differences between two choices of forward models for optical measurements in a cuvette, either Monte-Carlo or diffusion theory. A discrepancy between the two was found, which leads to an error of 10 % in µa and no error in µ's when Monte-Carlo was used to generate data and diffusion theory used to invert it. This result highlights the importance of which model is chosen for the inverse problem when this method is implemented in practice. Implementations would need to evaluate different models against ground truths to identify the optimal method for the measurement of absolute optical properties in a cuvette.
In this work, a miniaturized heterodyning FD-NIRS instrument was presented. The device uses a dual slope probe, which removes the need for pre-calibration. The low-footprint system consists of only the circuit board, the probe and a Raspberry-Pi. Four lasers (685 nm and 830 nm) and two avalanche photodiodes are used, where the lasers are modulated with 80 MHz and the APD signals are amplified and downconverted by the analog front end of the instrument: a custom designed fully differential ASIC in 130 nm CMOS technology. Solid phantom measurements revealed <9% error and significant stability for long-term measurements.
We propose novel frequency-domain data types, that show hybrid features to those of phase and AC intensity, i.e., better CNR features than phase data while preserving preferential sensitivity to deep tissue regions (like phase data). We show the CNR features of some of the novel data types in the dual-slope source-detector arrangement in the semi-infinite homogeneous medium and in the two-layer geometries. The results show that these novel data types indeed may have some hybrid features of AC and phase and may have a potential application in imaging of tissue.
SignificanceThis 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.AimTo 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).ApproachTheoretical 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.ResultsThe 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.ConclusionsDS 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.
Functional Near-InfraRed Spectroscopy (fNIRS) measures cerebral hemodynamics associated with brain activation. Non-invasive optical measurements of cerebral hemodynamics are often confounded by superficial, extra-cerebral hemodynamics and by instrumental and motion artifacts. These confounds are especially prominent in optical intensity data collected at a single source-detector distance. Alternatively, slope methods and frequency-domain measurements of the phase of photon-density waves have been proposed. Here, we first demonstrate the ability of a special slope method (dual-slope) to efficiently suppress instrumental artifacts. Then, a dual-slope imaging array is utilized to generate and compare single-distance and dual-slope intensity and phase data collected on the visual cortex of a human subject during a contrast reversing visual stimulation protocol. The measured hemodynamic traces associated with visual stimulation exhibit a larger amplitude when they are derived from dual-slope versus single-distance data, and from phase versus intensity data. In particular, the functional hemodynamics obtained from dual-slope phase data feature the largest amplitude. These results indicate the greater sensitivity to brain tissue achieved by dual-slope versus single-distance data, and by phase versus intensity data. The conclusion of this work is that dual-slope intensity (in continuous-wave fNIRS) and dual-slope or single-distance phase (in frequency-domain fNIRS) appear to be most effective for functional brain measurements, with the significant practical advantage offered by the minimal sensitivity of dual-slope measurements to a variety of artifacts.
KEYWORDS: Absorption, Chromophores, Calibration, Diffuse reflectance spectroscopy, Spectroscopy, In vivo imaging, Data modeling, Tissues, Scattering, Near infrared
We present a calibration-free instrument to measure absolute broadband absorption spectra of biological tissue. Initial measurements in skeletal muscle show that the fit to the data improves by introducing a spectrally flat absorption background.
We have recently introduced a Dual-Slope (DS) method implemented with Frequency-Domain (FD) NearInfraRed Spectroscopy (NIRS). Its chief advantages are a preferential sensitivity to deeper tissue and the suppression of instrumental artifacts. Thus-far, the work using the DS method has focused on local measurements of tissue hemodynamics. The next step in the development of DS is the measurement of spatially resolved absorption changes of tissue in vivo. To achieve this, we designed a DS imaging array for applications on human tissue. We utilized this array to measure maps of absolute optical properties in human skeletal muscle, and muscle hemodynamics during venous occlusion. In each case, spatial maps were created. The maps of baseline absolute optical properties showed higher scattering in connective tissue and higher absorption in muscle tissue. The analysis of hemodynamics found a greater blood accumulation during venous occlusion in muscle. Overall, muscle hemodynamics were shown to be spatially variable over a large area, suggesting the importance of imaging (as opposed to single-location) measurements. The preliminary data on human subjects with this new DS imaging array pave the way for applications in functional NIRS (fNIRS) for mapping brain activation.
In a study on one patient during hemodialysis, we used near-infrared spectroscopy (NIRS) to measure coherent oscillations of cerebral concentrations of oxyhemoglobin ([HbO2]), deoxyhemoglobin ([Hb]), and total-hemoglobin ([HbT]) induced by systemic oscillations in mean arterial pressure (MAP) at a frequency of 0.07 Hz. During hemodialysis, we observed that the phase of [Hb] versus [HbO2] becomes less negative, whereas the phase of [HbT] versus MAP becomes more negative. By applying a quantitative hemodynamic model, we assign these phase changes to an increase in venous blood transit time and a less effective cerebral autoregulation during the hemodialysis process.
One of the chief applications of diffuse optical spectroscopy is the measurement of chromophore concentrations in biological tissue, which requires measurements of tissue absorption. To achieve absolute absorption measurements, two chief confounds must be accounted for: instrumental contributions and tissue scattering. To account for instrumental contributions, a preliminary calibration on a phantom of known optical properties is typically done. The need for a calibration is eliminated by self-calibrating or dual-slope techniques using specially designed probe geometries. A technique that is capable of measuring tissue scattering is frequency domain near-infrared spectroscopy. However, it is typically not implemented for a spectrum of wavelengths due to instrumental complexity. Here we present a technique that combines self-calibrating frequency-domain at two wavelengths, to account for tissue scattering, and dual-slope continuous-wave broadband diffuse reflectance spectroscopy to achieve spectral measurements of absolute absorption between 600 nm and 1064 nm without any need for calibration. We apply this technique to two human tissues in vivo to determine concentrations of oxy-hemoglobin, deoxy-hemoglobin, lipids, and water. We found that the quality of the spectral fits may be significantly improved by the inclusion of a wavelength-independent background absorption. This leads to a discussion on the origin of this background absorption, and on the meaning of the chromophore concentrations that are recovered from spectral analysis. Current work is seeking to further understand and possibly correct for this apparent background absorption.
In this work we provide some examples of sensitivity of the dual slope method to localized absorption changes in the layered geometry. Reasonably, this model geometry better represents many types of tissue. The sensitivity is shown in a two- and three-layer geometry for alternating current (AC) and phase data for both point-like and layered-like absorption perturbations. Contrary to the homogeneous medium geometry, where the ratio of deep to superficial tissue sensitivity of phase is always greater than that of AC, this is not always the case in the layered geometry. Therefore, depending on the targeted tissue, subject and protocol, in some cases it might be preferable to use AC dual-slopes, whereas in other cases phase dual-slope may be a better choice.
The use of phase (Φ) data collected in Frequency-Domain Near-InfraRed Spectroscopy (FD-NIRS) has not been widespread in measurements of skeletal muscle and has mainly been applied to measure absolute optical properties. We show that single-distance (SD) Φ has a deeper sensitivity compared to SD intensity (I) and can be more sensitive to oxygen consumption in skeletal muscle underneath superficial adipose tissue. We also show the potential benefit of single-slope (SS) or dual-slope (DS) I or Φ in muscle studies.
We introduce a novel method to enhance the sensitivity of near-infrared spectroscopy (NIRS) to deep tissue (i.e. brain cortex, skeletal muscle, etc.) in non-invasive diffuse optical measurements. Our method relies on the collection of the phase of photon-density waves, launched by intensity-modulated light in frequency-domain NIRS, from two paired sets of multi-distance data. The two sets of data are combined into a phase dual-slope, which features a stronger sensitivity to deeper vs. superficial tissue. For typical conditions of functional NIRS, the maximum sensitivity of phase dual-slopes is at a depth of ~11 mm, which approaches the depth of cortical tissue.
Near-infrared (NIR) spectroscopic imaging of wounds has been performed by past researchers to obtain tissue oxygenation at discrete point locations. We had developed a near-infrared optical scanner (NIROS) that performs noncontact NIR spectroscopic (NIRS) imaging to provide 2D tissue oxygenation maps of the entire wounds. Regions of changed oxygenation have to be demarcated and registered with respect to visual white light images of the wound. Herein, a semi-automatic image segmentation and co-registration approach using machine learning has been developed to differentiate regions of changed tissue oxygenation. A registration technique was applied using a transformation matrix approach using specific markers across the white light image and the NIR images (or tissue oxygenation maps). This allowed for physiological changes observed from hemodynamic changes to be observed in the RGB white light image as well. Semi-automated segmentation techniques employing graph cuts algorithms was implemented to demarcate the 2D tissue oxygenation maps depicting regions of increased or decreased oxygenation and further coregistered onto the white light images. The developed registration technique was validated via phantom studies (both flat and curved phantoms) and in-vivo studies on controls, demonstrating an accuracy >97%. The technique was further implemented on wounds (here, diabetic foot ulcers) across weeks of treatment. Regions of decreased oxygenation were demarcated, and its area estimated and co-registered in comparison to the clinically demarcated wound area. Future work involves the development of automated machine learning approaches of image analysis for clinicians to obtain real-time co-registered clinical and subclinical assessments of the wound.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.