Significance:Functional near-infrared spectroscopy (fNIRS) is a noninvasive technology that uses low levels of nonionizing light in the range of red and near-infrared to record changes in the optical absorption and scattering of the underlying tissue that can be used to infer blood flow and oxygen changes during brain activity. The challenges and difficulties of reconstructing spatial images of hemoglobin changes from fNIRS data are mainly caused by the illposed nature of the optical inverse model.Aim:We describe a Bayesian approach combining several lasso-based regularizations to apply anatomy-prior information to solving the inverse model.Approach:We built a Bayesian hierarchical model to solve the Bayesian adaptive fused sparse overlapping group lasso (Ba-FSOGL) model. The method is evaluated and validated using simulation and experimental datasets.Results:We apply this approach to the simulation and experimental datasets to reconstruct a known brain activity. The reconstructed images and statistical plots are shown.Conclusion:We discuss the adaptation of this method to fNIRS data and demonstrate that this approach provides accurate image reconstruction with a low false-positive rate, through numerical simulations and application to experimental data collected during motor and sensory tasks.
KEYWORDS: Near infrared spectroscopy, Data acquisition, Standards development, Software development, Neuroimaging, Neurophotonics, Design and modelling, MATLAB, Data storage, Compliance
SignificanceFunctional near-infrared spectroscopy (fNIRS) is a popular neuroimaging technique with proliferating hardware platforms, analysis approaches, and software tools. There has not been a standardized file format for storing fNIRS data, which has hindered the sharing of data as well as the adoption and development of software tools.AimWe endeavored to design a file format to facilitate the analysis and sharing of fNIRS data that is flexible enough to meet the community’s needs and sufficiently defined to be implemented consistently across various hardware and software platforms.ApproachThe shared NIRS format (SNIRF) specification was developed in consultation with the academic and commercial fNIRS community and the Society for functional Near Infrared Spectroscopy.ResultsThe SNIRF specification defines a format for fNIRS data acquired using continuous wave, frequency domain, time domain, and diffuse correlation spectroscopy devices.ConclusionsWe present the SNIRF along with validation software and example datasets. Support for reading and writing SNIRF data has been implemented by major hardware and software platforms, and the format has found widespread use in the fNIRS community.
KEYWORDS: Autoregressive models, Physiology, Data modeling, Motion models, Statistical analysis, Interference (communication), Statistical modeling, Neurophotonics, Brain, Signal to noise ratio
Significance: Resting-state functional connectivity (RSFC) analyses of functional near-infrared spectroscopy (fNIRS) data reveal cortical connections and networks across the brain. Motion artifacts and systemic physiology in evoked fNIRS signals present unique analytical challenges, and methods that control for systemic physiological noise have been explored. Whether these same methods require modification when applied to resting-state fNIRS (RS-fNIRS) data remains unclear.Aim: We systematically examined the sensitivity and specificity of several RSFC analysis pipelines to identify the best methods for correcting global systemic physiological signals in RS-fNIRS data.Approach: Using numerically simulated RS-fNIRS data, we compared the rates of true and false positives for several connectivity analysis pipelines. Their performance was scored using receiver operating characteristic analysis. Pipelines included partial correlation and multivariate Granger causality, with and without short-separation measurements, and a modified multivariate causality model that included a non-traditional zeroth-lag cross term. We also examined the effects of pre-whitening and robust statistical estimators on performance.Results: Consistent with previous work on bivariate correlation models, our results demonstrate that robust statistics and pre-whitening are effective methods to correct for motion artifacts and autocorrelation in the fNIRS time series. Moreover, we found that pre-filtering using principal components extracted from short-separation fNIRS channels as part of a partial correlation model was most effective in reducing spurious correlations due to shared systemic physiology when the two signals of interest fluctuated synchronously. However, when there was a temporal lag between the signals, a multivariate Granger causality test incorporating the short-separation channels was better. Since it is unknown if such a lag exists in experimental data, we propose a modified version of Granger causality that includes the non-traditional zeroth-lag term as a compromising solution.Conclusions: A combination of pre-whitening, robust statistical methods, and partial correlation in the processing pipeline to reduce autocorrelation, motion artifacts, and global physiology are suggested for obtaining statistically valid connectivity metrics with RS-fNIRS. Further studies should validate the effectiveness of these methods using human data.
Significance: Electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) are both commonly used methodologies for neuronal source reconstruction. While EEG has high temporal resolution (millisecond-scale), its spatial resolution is on the order of centimeters. On the other hand, in comparison to EEG, fNIRS, or diffuse optical tomography (DOT), when used for source reconstruction, can achieve relatively high spatial resolution (millimeter-scale), but its temporal resolution is poor because the hemodynamics that it measures evolve on the order of several seconds. This has important neuroscientific implications: e.g., if two spatially close neuronal sources are activated sequentially with only a small temporal separation, single-modal measurements using either EEG or DOT alone would fail to resolve them correctly.
Aim: We attempt to address this issue by performing joint EEG and DOT neuronal source reconstruction.
Approach: We propose an algorithm that utilizes DOT reconstruction as the spatial prior of EEG reconstruction, and demonstrate the improvements using simulations based on the ICBM152 brain atlas.
Results: We show that neuronal sources can be reconstructed with higher spatiotemporal resolution using our algorithm than using either modality individually. Further, we study how the performance of the proposed algorithm can be affected by the locations of the neuronal sources, and how the performance can be enhanced by improving the placement of EEG electrodes and DOT optodes.
Conclusions: We demonstrate using simulations that two sources separated by 2.3-3.3 cm and 50 ms can be recovered accurately using the proposed algorithm by suitably combining EEG and DOT, but not by either in isolation. We also show that the performance can be enhanced by optimizing the electrode and optode placement according to the locations of the neuronal sources.
Significance: Isolating task-evoked brain signals from background physiological noise (e.g., cardiac, respiratory, and blood pressure fluctuations) poses a major challenge for the analysis of functional near-infrared spectroscopy (fNIRS) data.
Aim: The performance of several analytic methods to separate background physiological noise from brain activity including spatial and temporal filtering, regression, component analysis, and the use of short-separation (SS) measurements were quantitatively compared.
Approach: Using experimentally recorded background signals (breath-hold task), receiver operating characteristics simulations were performed by adding various levels of additive synthetic “brain” responses in order to examine the sensitivity and specificity of several previously proposed analytic approaches.
Results: We found that the use of SS fNIRS channels as regressors of no-interest within a linear regression model was the best performing approach examined. Furthermore, we found that the addition of all available SS data, including all recorded channels and both hemoglobin species, improved the method performance despite the additional degrees-of-freedom of the models. When SS data were not available, we found that principal component filtering using a separate baseline scan was the best alternative.
Conclusions: The use of multiple SS measurements as regressors of no interest implemented in a robust, iteratively prewhitened, general linear model has the best performance of the tested existing methods.
Significance: Functional near-infrared spectroscopy (fNIRS) uses surface-placed light sources and detectors to record underlying changes in the brain due to fluctuations in hemoglobin levels and oxygenation. Since these measurements are recorded from the surface of the scalp, the mapping from underlying regions-of-interest (ROIs) in the brain space to the fNIRS channel space measurements depends on the registration of the sensors, the anatomy of the head/brain, and the sensitivity of these diffuse measurements through the tissue. However, small displacements in the probe position can change the distribution of recorded brain activity across the fNIRS measurements.
Aim: We propose an approach using either individual or atlas-based brain-space anatomical information to define ROI-based statistical hypotheses to test the null involvement of specific regions, which allows us to test the analogous ROI across subjects while adjusting for fNIRS probe placement and sensitivity differences due to head size variations without a localizer task.
Approach: We use the optical forward model to project the underlying brain-space ROI into a tapered contrast vector, which defines the relative weighting of the fNIRS channels contributing to the ROI and allows us to test the null hypothesis of no brain activity in this region during a functional task. We demonstrate this method through simulation and compare the sensitivity-specificity of this approach to other conventional methods.
Results: We examine the performance of this method in the scenario where head size and probe registration are both an accurately known parameters and where this is subject to unknown experimental errors. This method is compared with the performance of the conventional method using 364 different simulation parameter combinations.
Conclusion: The proposed method is always recommended in ROI-based analysis, since it significantly improves the analysis performance without a localizer task, wherever the fNIRS probe registration is known or unknown.
Functional near-infrared spectroscopy (fNIRS) is a noninvasive brain imaging technique to measure evoked changes in cerebral blood oxygenation. In many evoked-task studies, the analysis of fNIRS experiments is based on a temporal linear regression model, which includes block-averaging, deconvolution, and canonical analysis models. The statistical parameters of this model are then spatially mapped across fNIRS measurement channels to infer brain activity. The trade-offs in sensitivity and specificity of using variations of canonical or deconvolution/block-average models are unclear. We quantitatively investigate how the choice of basis set for the regression linear model affects the sensitivity and specificity of fNIRS analysis in the presence of variability or systematic bias in underlying evoked response. For statistical parametric mapping of amplitude-based hypotheses, we conclude that these models are fairly insensitive to the parameters of the regression basis for task durations >10 s and we report the highest sensitivity-specificity results using a low degree-of-freedom canonical model under these conditions. For shorter duration task (<10 s), the signal-to-noise ratio of the data is also important in this decision and we find that deconvolution or block-averaging models outperform the canonical models at high signal-to-noise ratio but not at lower levels.
KEYWORDS: Brain, Head, Near infrared spectroscopy, Neurophotonics, Visualization, Monte Carlo methods, Tissue optics, Magnetic resonance imaging, Skull, Sensors
Functional near-infrared spectroscopy (fNIRS) is a noninvasive brain imaging technique that uses scalp-placed light sensors to measure evoked changes in cerebral blood oxygenation. The portability, low overhead cost, and ability to use this technology under a wide range of experimental environments make fNIRS well-suited for studies involving infants and children. However, since fNIRS does not directly provide anatomical or structural information, these measurements may be sensitive to individual or group level differences associated with variations in head size, depth of the brain from the scalp, or other anatomical factors affecting the penetration of light into the head. This information is generally not available in pediatric populations, which are often the target of study for fNIRS. Anatomical magnetic resonance imaging information from 90 school-age children (5 to 11 years old) was used to quantify the expected effect on fNIRS measures of variations in cerebral and extracerebral structure. Monte Carlo simulations of light transport in tissue were used to estimate differential and partial optical pathlengths at 690, 780, 808, 830, and 850 nm and their variations with age, sex, and head size. This work provides look-up tables of these values and general guidance for future investigations using fNIRS sans anatomical information in this child population.
Functional near-infrared spectroscopy (fNIRS) is a noninvasive neuroimaging technique that uses low levels of red to near-infrared light to measure changes in cerebral blood oxygenation. Spontaneous (resting state) functional connectivity (sFC) has become a critical tool for cognitive neuroscience for understanding task-independent neural networks, revealing pertinent details differentiating healthy from disordered brain function, and discovering fluctuations in the synchronization of interacting individuals during hyperscanning paradigms. Two of the main challenges to sFC-NIRS analysis are (i) the slow temporal structure of both systemic physiology and the response of blood vessels, which introduces false spurious correlations, and (ii) motion-related artifacts that result from movement of the fNIRS sensors on the participants’ head and can introduce non-normal and heavy-tailed noise structures. In this work, we systematically examine the false-discovery rates of several time- and frequency-domain metrics of functional connectivity for characterizing sFC-NIRS. Specifically, we detail the modifications to the statistical models of these methods needed to avoid high levels of false-discovery related to these two sources of noise in fNIRS. We compare these analysis procedures using both simulated and experimental resting-state fNIRS data. Our proposed robust correlation method has better performance in terms of being more reliable to the noise outliers due to the motion artifacts.
Functional near-infrared spectroscopy (fNIRS) is a noninvasive neuroimaging technique used to measure changes in oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb) in the brain. In this study, we present a decomposition approach based on single-channel independent component analysis (scICA) to investigate the contribution of physiological noise to fNIRS signals during rest. Single-channel ICA is an underdetermined decomposition method, which separates a single time series into components containing nonredundant spectral information. Using scICA, fNIRS signals from a total of 17 subjects were decomposed into the constituent physiological components. The percentage contribution of the classes of physiology to the fNIRS signals including low-frequency (LF) fluctuations, respiration, and cardiac oscillations was estimated using spectral domain classification methods. Our results show that LF oscillations accounted for 40% to 55% of total power of both the oxy-Hb and deoxy-Hb signals. Respiration and its harmonics accounted for 10% to 30% of the power, and cardiac pulsations and cardio-respiratory components accounted for 10% to 30%. We describe this scICA method for decomposing fNIRS signals, which unlike other approaches to spatial covariance reduction is applicable to both single- or multiple-channel fNIRS signals and discuss how this approach allows functionally distinct sources of noise with disjoint spectral support to be separated from obscuring systemic physiology.
Functional near-infrared spectroscopy (fNIRS) is a relatively low-cost, portable, noninvasive neuroimaging technique for measuring task-evoked hemodynamic changes in the brain. Because fNIRS can be applied to a wide range of populations, such as children or infants, and under a variety of study conditions, including those involving physical movement, gait, or balance, fNIRS data are often confounded by motion artifacts. Furthermore, the high sampling rate of fNIRS leads to high temporal autocorrelation due to systemic physiology. These two factors can reduce the sensitivity and specificity of detecting hemodynamic changes. In a previous work, we showed that these factors could be mitigated by autoregressive-based prewhitening followed by the application of an iterative reweighted least squares algorithm offline. This current work extends these same ideas to real-time analysis of brain signals by modifying the linear Kalman filter, resulting in an algorithm for online estimation that is robust to systemic physiology and motion artifacts. We evaluated the performance of the proposed method via simulations of evoked hemodynamics that were added to experimental resting-state data, which provided realistic fNIRS noise. Last, we applied the method post hoc to data from a standing balance task. Overall, the new method showed good agreement with the analogous offline algorithm, in which both methods outperformed ordinary least squares methods.
Functional near-infrared spectroscopy (fNIRS) is a noninvasive neuroimaging technique that uses low levels of light to measure changes in cerebral blood oxygenation levels. In the majority of NIRS functional brain studies, analysis of this data is based on a statistical comparison of hemodynamic levels between a baseline and task or between multiple task conditions by means of a linear regression model: the so-called general linear model. Although these methods are similar to their implementation in other fields, particularly for functional magnetic resonance imaging, the specific application of these methods in fNIRS research differs in several key ways related to the sources of noise and artifacts unique to fNIRS. In this brief communication, we discuss the application of linear regression models in fNIRS and the modifications needed to generalize these models in order to deal with structured (colored) noise due to systemic physiology and noise heteroscedasticity due to motion artifacts. The objective of this work is to present an overview of these noise properties in the context of the linear model as it applies to fNIRS data. This work is aimed at explaining these mathematical issues to the general fNIRS experimental researcher but is not intended to be a complete mathematical treatment of these concepts.
The relationship between measurements of cerebral blood oxygenation and neuronal activity is highly complex and depends on both neurovascular and neurometabolic biological coupling. While measurements of blood oxygenation changes via optical and MRI techniques have been developed to map functional brain activity, there is evidence that the specific characteristics of these signals are sensitive to the underlying vascular physiology and structure of the brain. Since baseline blood flow and oxygen saturation may vary between sessions and across subjects, functional blood oxygenation changes may be a less reliable indicator of brain activity in comparison to blood flow and metabolic changes. In this work, we use a biomechanical model to examine the relationships between neural, vascular, metabolic, and hemodynamic responses to parametric whisker stimulation under both normal and hypercapnic conditions in a rat model. We find that the relationship between neural activity and oxy- and deoxyhemoglobin changes is sensitive to hypercapnia-induced changes in baseline cerebral blood flow. In contrast, the underlying relationships between evoked neural activity, blood flow, and model-estimated oxygen metabolism changes are unchanged by the hypercapnic challenge. We conclude that evoked changes in blood flow and cerebral oxygen metabolism are more closely associated with underlying evoked neuronal responses.
In the last two decades, both diffuse optical tomography (DOT) and blood oxygen level dependent (BOLD)-based functional magnetic resonance imaging (fMRI) methods have been developed as noninvasive tools for imaging evoked cerebral hemodynamic changes in studies of brain activity. Although these two technologies measure functional contrast from similar physiological sources, i.e., changes in hemoglobin levels, these two modalities are based on distinct physical and biophysical principles leading to both limitations and strengths to each method. In this work, we describe a unified linear model to combine the complimentary spatial, temporal, and spectroscopic resolutions of concurrently measured optical tomography and fMRI signals. Using numerical simulations, we demonstrate that concurrent optical and BOLD measurements can be used to create cross-calibrated estimates of absolute micromolar deoxyhemoglobin changes. We apply this new analysis tool to experimental data acquired simultaneously with both DOT and BOLD imaging during a motor task, demonstrate the ability to more robustly estimate hemoglobin changes in comparison to DOT alone, and show how this approach can provide cross-calibrated estimates of hemoglobin changes. Using this multimodal method, we estimate the calibration of the 3tesla BOLD signal to be −0.55%±0.40% signal change per micromolar change of deoxyhemoglobin.
We describe a near-infrared spectroscopy (NIRS) method to noninvasively measure relative changes in the pulsate components of cerebral blood flow (pCBF) and volume (pCBV) from the shape of heartbeat oscillations. We present a model that is used and data to show the feasibility of the method. We use a continuous-wave NIRS system to measure the arterial oscillations originating in the brains of piglets. Changes in the animals' CBF are induced by adding CO2 to the breathing gas. To study the influence of scalp on our measurements, comparative, invasive measurements are performed on one side of the head simultaneously with noninvasive measurements on the other side. We also did comparative measurements of CBF using a laser Doppler system to validate the results of our method. The results indicate that for sufficient source-detector separation, the signal contribution of the scalp is minimal and the measurements are representative of the cerebral hemodynamics. Moreover, good correlation between the results of the laser Doppler system and the NIRS system indicate that the presented method is capable of measuring relative changes in CBF. Preliminary results show the potential of this NIRS method to measure pCBF and pCBV relative changes in neonatal pigs.
Akin to functional magnetic resonance imaging (fMRI), diffuse optical imaging (DOI) is a noninvasive method for measuring localized changes in hemoglobin levels within the brain. When combined with fMRI methods, multimodality approaches could offer an integrated perspective on the biophysics, anatomy, and physiology underlying each of the imaging modalities. Vital to the correct interpretation of such studies, control experiments to test the consistency of both modalities must be performed. Here, we compare DOI with blood oxygen level-dependent (BOLD) and arterial spin labeling fMRI-based methods in order to explore the spatial agreement of the response amplitudes recorded by these two methods. Rather than creating optical images by regularized, tomographic reconstructions, we project the fMRI image into optical measurement space using the optical forward problem. We report statistically better spatial correlation between the fMRI-BOLD response and the optically measured deoxyhemoglobin (R=0.71, p=1×10?7) than between the BOLD and oxyhemoglobin or total hemoglobin measures (R=0.38, p=0.04|0.37, p=0.05, respectively). Similarly, we find that the correlation between the ASL measured blood flow and optically measured total and oxyhemoglobin is stronger (R=0.73, p=5×10?6 and R=0.71, p=9×10?6, respectively) than the flow to deoxyhemoglobin spatial correlation (R=0.26, p=0.10).
KEYWORDS: Sensors, Head, Visualization, Diffuse optical imaging, Hemodynamics, Brain, Principal component analysis, Blood pressure, Signal to noise ratio, Imaging systems
Near-Infrared Spectroscopy (NIRS) and diffuse optical imaging (DOI) are increasingly used to detect hemodynamic changes in the cerebral cortex induced by brain activity. Until recently, the small number of optodes in NIRS instruments has hampered measurement of optical signals from diverse brain regions. Our new DOI system has 32 detectors and 32 sources; by arranging them in a specific pattern, we can cover most of the adult head. With the increased number of optodes, we can collect optical data from prefrontal, sensorimotor, and visual cortices in both hemispheres simultaneously. We describe the system and report system characterization measurements on phantoms as well as on human subjects at rest and during visual, motor, and cognitive stimulation. Taking advantage of the system's larger number of sources and detectors, we explored the spatiotemporal patterns of physiological signals during rest. These physiological signals, arising from cardiac, respiratory, and blood-pressure modulations, interfere with measurement of the hemodynamic response to brain stimulation. Whole-head optical measurements, in addition to providing maps of multiple brain regions' responses to brain activation, will enable better understandings of the physiological signals, ultimately leading to better signal processing algorithms to distinguish physiological signal clutter from brain activation signals.
KEYWORDS: Near infrared spectroscopy, Functional magnetic resonance imaging, Hemodynamics, Magnetic resonance imaging, Brain, Monte Carlo methods, Sensors, Spatial resolution, Neuroimaging, Photons
Near infrared spectroscopy (NIRS) has the ability to record, at high temporal resolution, hemodynamic changes within the brain during functional activity. Although alone, NIRS has a poorer spatial resolution compared to other imaging methods such as functional MRI (fMRI), multi-modality approaches, which attempt to fuse the spatial resolution of MRI with the hemoglobin oxygenation information and temporal resolution of NIRS, show promise to yielding better insight into the hemodynamic and metabolic response of the functional brain in future research. However, paramount to the development of these multi-modality approaches, proper control experiments to validate the correlation between NIRS and fMRI methods must be preformed. In this experiment, we have examined the spatial and temporal relationship between the NIRS measure of deoxy-hemoglobin and the fMRI blood oxygen level dependent (BOLD) signal. Here, we have modeled the propagation of light through realistic, tissue segmented, head models for each of five subjects. Using these sensitivity profiles, we predicted the measurement of deoxy-hemoglobin for each individual NIRS source-detector pair from the projection of the volume-wise fMRI BOLD changes, thus allowing a quantitative spatial and temporal comparison between NIRS and fMRI. We report a linear correlation of R = 0.73 (p < 2x10 -8) between the spatial profiles between the NIRS measure of deoxy-hemoglobin and BOLD signal. We also report a temporal correlation of R=0.88 (p<9x10 -18) between the region-of-interest averaged responses using the projected BOLD response.
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