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1.  Simulation of Near-Infrared Light Absorption Considering Individual Head and Prefrontal Cortex Anatomy: Implications for Optical Neuroimaging 
PLoS ONE  2011;6(10):e26377.
Functional near-infrared spectroscopy (fNIRS) is an established optical neuroimaging method for measuring functional hemodynamic responses to infer neural activation. However, the impact of individual anatomy on the sensitivity of fNIRS measuring hemodynamics within cortical gray matter is still unknown. By means of Monte Carlo simulations and structural MRI of 23 healthy subjects (mean age: years), we characterized the individual distribution of tissue-specific NIR-light absorption underneath 24 prefrontal fNIRS channels. We, thereby, investigated the impact of scalp-cortex distance (SCD), frontal sinus volume as well as sulcal morphology on gray matter volumes () traversed by NIR-light, i.e. anatomy-dependent fNIRS sensitivity. The NIR-light absorption between optodes was distributed describing a rotational ellipsoid with a mean penetration depth of considering the deepest of light. Of the detected photon packages scalp and bone absorbed and absorbed of the energy. The mean volume was negatively correlated () with the SCD and frontal sinus volume () and was reduced by in subjects with relatively large compared to small frontal sinus. Head circumference was significantly positively correlated with the mean SCD () and the traversed frontal sinus volume (). Sulcal morphology had no significant impact on . Our findings suggest to consider individual SCD and frontal sinus volume as anatomical factors impacting fNIRS sensitivity. Head circumference may represent a practical measure to partly control for these sources of error variance.
doi:10.1371/journal.pone.0026377
PMCID: PMC3200329  PMID: 22039475
2.  Depth Sensitivity and Source-Detector Separations for Near Infrared Spectroscopy Based on the Colin27 Brain Template 
PLoS ONE  2013;8(8):e66319.
Understanding the spatial and depth sensitivity of non-invasive near-infrared spectroscopy (NIRS) measurements to brain tissue–i.e., near-infrared neuromonitoring (NIN) – is essential for designing experiments as well as interpreting research findings. However, a thorough characterization of such sensitivity in realistic head models has remained unavailable. In this study, we conducted 3,555 Monte Carlo (MC) simulations to densely cover the scalp of a well-characterized, adult male template brain (Colin27). We sought to evaluate: (i) the spatial sensitivity profile of NIRS to brain tissue as a function of source-detector separation, (ii) the NIRS sensitivity to brain tissue as a function of depth in this realistic and complex head model, and (iii) the effect of NIRS instrument sensitivity on detecting brain activation. We found that increasing the source-detector (SD) separation from 20 to 65 mm provides monotonic increases in sensitivity to brain tissue. For every 10 mm increase in SD separation (up to ∼45 mm), sensitivity to gray matter increased an additional 4%. Our analyses also demonstrate that sensitivity in depth (S) decreases exponentially, with a “rule-of-thumb” formula S = 0.75*0.85depth. Thus, while the depth sensitivity of NIRS is not strictly limited, NIN signals in adult humans are strongly biased towards the outermost 10–15 mm of intracranial space. These general results, along with the detailed quantitation of sensitivity estimates around the head, can provide detailed guidance for interpreting the likely sources of NIRS signals, as well as help NIRS investigators design and plan better NIRS experiments, head probes and instruments.
doi:10.1371/journal.pone.0066319
PMCID: PMC3731322  PMID: 23936292
3.  Patient-oriented simulation based on Monte Carlo algorithm by using MRI data 
Background
Although Monte Carlo simulations of light propagation in full segmented three-dimensional MRI based anatomical models of the human head have been reported in many articles. To our knowledge, there is no patient-oriented simulation for individualized calibration with NIRS measurement. Thus, we offer an approach for brain modeling based on image segmentation process with in vivo MRI T1 three-dimensional image to investigate the individualized calibration for NIRS measurement with Monte Carlo simulation.
Methods
In this study, an individualized brain is modeled based on in vivo MRI 3D image as five layers structure. The behavior of photon migration was studied for this individualized brain detections based on three-dimensional time-resolved Monte Carlo algorithm. During the Monte Carlo iteration, all photon paths were traced with various source-detector separations for characterization of brain structure to provide helpful information for individualized design of NIRS system.
Results
Our results indicate that the patient-oriented simulation can provide significant characteristics on the optimal choice of source-detector separation within 3.3 cm of individualized design in this case. Significant distortions were observed around the cerebral cortex folding. The spatial sensitivity profile penetrated deeper to the brain in the case of expanded CSF. This finding suggests that the optical method may provide not only functional signal from brain activation but also structural information of brain atrophy with the expanded CSF layer. The proposed modeling method also provides multi-wavelength for NIRS simulation to approach the practical NIRS measurement.
Conclusions
In this study, the three-dimensional time-resolved brain modeling method approaches the realistic human brain that provides useful information for NIRS systematic design and calibration for individualized case with prior MRI data.
doi:10.1186/1475-925X-11-21
PMCID: PMC3355000  PMID: 22510474
Patient-oriented simulation; Time-resolved Monte Carlo; Brain modeling; Spatial sensitivity profile
4.  The physiological origin of task-evoked systemic artefacts in functional near infrared spectroscopy 
Neuroimage  2012;61(1):70-81.
A major methodological challenge of functional near-infrared spectroscopy (fNIRS) is its high sensitivity to haemodynamic fluctuations in the scalp. Superficial fluctuations contribute on the one hand to the physiological noise of fNIRS, impairing the signal-to-noise ratio, and may on the other hand be erroneously attributed to cerebral changes, leading to false positives in fNIRS experiments. Here we explore the localisation, time course and physiological origin of task-evoked superficial signals in fNIRS and present a method to separate them from cortical signals. We used complementary fNIRS, fMRI, MR-angiography and peripheral physiological measurements (blood pressure, heart rate, skin conductance and skin blood flow) to study activation in the frontal lobe during a continuous performance task. The General Linear Model (GLM) was applied to analyse the fNIRS data, which included an additional predictor to account for systemic changes in the skin.
We found that skin blood volume strongly depends on the cognitive state and that sources of task-evoked systemic signals in fNIRS are co-localized with veins draining the scalp. Task-evoked superficial artefacts were mainly observed in concentration changes of oxygenated haemoglobin and could be effectively separated from cerebral signals by GLM analysis. Based on temporal correlation of fNIRS and fMRI signals with peripheral physiological measurements we conclude that the physiological origin of the systemic artefact is a task-evoked sympathetic arterial vasoconstriction followed by a decrease in venous volume.
Since changes in sympathetic outflow accompany almost any cognitive and emotional process, we expect scalp vessel artefacts to be present in a wide range of fNIRS settings used in neurocognitive research. Therefore a careful separation of fNIRS signals originating from activated brain and from scalp is a necessary precondition for unbiased fNIRS brain activation maps.
Highlights
► Task-evoked changes in the skin blood volume induce artefacts in fNIRS signals. ► Artefacts result from a venous volume decrease due to sympathetic vasoconstriction. ► This phenomenon might induce false positives in fNIRS experiments on the forehead.
doi:10.1016/j.neuroimage.2012.02.074
PMCID: PMC3348501  PMID: 22426347
Time-domain optical brain imaging; Systemic changes; Skin blood flow; Periphery physiology; fMRI; Frontal lobe
5.  Short separation channel location impacts the performance of short channel regression in NIRS 
Neuroimage  2011;59(3):2518-2528.
Near-Infrared Spectroscopy (NIRS) allows the recovery of cortical oxy-and deoxyhemoglobin changes associated with evoked brain activity. NIRS is a back-reflection measurement making it very sensitive to the superficial layers of the head, i.e. the skin and the skull, where systemic interference occurs. As a result, the NIRS signal is strongly contaminated with systemic interference of superficial origin. A recent approach to overcome this problem has been the use of additional short source-detector separation optodes as regressors. Since these additional measurements are mainly sensitive to superficial layers in adult humans, they can be used to remove the systemic interference present in longer separation measurements, improving the recovery of the cortical hemodynamic response function (HRF). One question that remains to answer is whether or not a short separation measurement is required in close proximity to each long separation NIRS channel. Here, we show that the systemic interference occurring in the superficial layers of the human head is inhomogeneous across the surface of the scalp. As a result, the improvement obtained by using a short separation optode decreases as the relative distance between the short and the long measurement is increased. NIRS data was acquired on 6 human subjects both at rest and during a motor task consisting of finger tapping. The effect of distance between the short and the long channel was first quantified by recovering a synthetic hemodynamic response added over the resting-state data. The effect was also observed in the functional data collected during the finger tapping task. Together, these results suggest that the short separation measurement must be located as close as 1.5 cm from the standard NIRS channel in order to provide an improvement which is of practical use. In this case, the improvement in Contrast-to-Noise Ratio (CNR) compared to a standard General Linear Model (GLM) procedure without using any small separation optode reached 50 % for HbO and 100 % for HbR. Using small separations located farther than 2 cm away resulted in mild or negligible improvements only.
doi:10.1016/j.neuroimage.2011.08.095
PMCID: PMC3254723  PMID: 21945793
Near-Infrared Spectroscopy; Systemic Interference; Short Optode Separations; Kalman filtering
6.  A quantitative comparison of NIRS and fMRI across multiple cognitive tasks 
NeuroImage  2010;54(4):2808-2821.
Near infrared spectroscopy (NIRS) is an increasingly popular technology for studying brain function. NIRS presents several advantages relative to functional magnetic resonance imaging (fMRI), such as measurement of concentration changes in both oxygenated- and deoxygenated hemoglobin, finer temporal resolution, and ease of administration, as well as disadvantages, most prominently inferior spatial resolution and decreased signal-to-noise ratio (SNR). While fMRI has become the gold standard for in vivo imaging of the human brain, in practice NIRS is a more convenient and less expensive technology than fMRI. It is therefore of interest to many researchers how NIRS compares to fMRI in studies of brain function. In the present study we scanned participants with simultaneous NIRS and fMRI on a battery of cognitive tasks, placing NIRS probes over both frontal and parietal brain regions. We performed detailed comparisons of the signals in both temporal and spatial domains. We found that NIRS signals have significantly weaker SNR, but are nonetheless often highly correlated with fMRI measurements. Both SNR and the distance between the scalp and the brain contributed to variability in the NIRS/fMRI correlations. In the spatial domain, we found that a photon path forming an ellipse between the NIRS emitter and detector correlated most strongly with the BOLD response. Taken together these findings suggest that, while NIRS can be an appropriate substitute for fMRI for studying brain activity related to cognitive tasks, care should be taken when designing studies with NIRS to ensure that: 1) the spatial resolution is adequate for answering the question of interest and 2) the design accounts for weaker SNR, especially in brain regions more distal from the scalp.
doi:10.1016/j.neuroimage.2010.10.069
PMCID: PMC3021967  PMID: 21047559
7.  Coregistering functional near-infrared spectroscopy with underlying cortical areas in infants 
Neurophotonics  2014;1(2):025006-.
Functional near-infrared spectroscopy (fNIRS) is becoming a popular tool in developmental neuroscience for mapping functional localized brain responses. However, as it cannot provide information about underlying anatomy, researchers have begun to conduct spatial registration of fNIRS channels to cortical anatomy in adults. The current work investigated this issue with infants by coregistering fNIRS and magnetic resonance imaging (MRI) data from 55 individuals. Our findings suggest that fNIRS channels can be reliably registered with regions in the frontal and temporal cortex of infants from 4 to 7 months of age. Although some macro-anatomical regions are difficult to consistently define, others are more stable and fNIRS channels on an age-appropriate MRI template are often consistent with individual infant MRIs. We have generated a standardized scalp surface map of fNIRS channel locators to reliably locate cortical regions for fNIRS developmental researchers. This new map can be used to identify the inferior frontal gyrus, superior temporal sulcus (STS) region [which includes the superior and middle temporal gyri (MTG) nearest to the STS], and MTG and temporal-parietal regions in 4- to 7-month-old infants. Future work will model data for the whole head, taking into account the properties of light transport in tissue, and expanding to different ages across development.
doi:10.1117/1.NPh.1.2.025006
PMCID: PMC4280679  PMID: 25558463
functional near-infrared spectroscopy; magnetic resonance imaging; coregistration; infancy; development
8.  Cerebral functional imaging using near-infrared spectroscopy during repeated performances of motor rehabilitation tasks tested on healthy subjects 
To investigate the relationship between the frontal and sensorimotor cortices and motor learning, hemodynamic responses were recorded from the frontal and sensorimotor cortices using functional near infrared spectroscopy (NIRS) while healthy subjects performed motor learning tasks used in rehabilitation medicine. Whole-head NIRS recordings indicated that response latencies in the anterior dorsomedial prefrontal cortex (aDMPFC) were shorter than in other frontal and parietal areas. Furthermore, the increment rate of the hemodynamic responses in the aDMPFC across the eight repeated trials significantly correlated with those in the other areas, as well as with the improvement rate of task performance across the 8 repeated trials. In the second experiment, to dissociate scalp- and brain-derived hemodynamic responses, hemodynamic responses were recorded from the head over the aDMPFC using a multi-distance probe arrangement. Six probes (a single source probe and 5 detectors) were linearly placed 6 mm apart from each of the neighboring probes. Using independent component analyses of hemodynamic signals from the 5 source-detector pairs, we dissociated scalp- and brain-derived components of the hemodynamic responses. Hemodynamic responses corrected for scalp-derived responses over the aDMPFC significantly increased across the 8 trials and correlated with task performance. In the third experiment, subjects were required to perform the same task with and without transcranial direct current stimulation (tDCS) of the aDMPFC before the task. The tDCS significantly improved task performance. These results indicate that the aDMPFC is crucial for improved performance in repetitive motor learning.
doi:10.3389/fnhum.2014.00292
PMCID: PMC4026732  PMID: 24860474
frontal pole; NIRS; rehabilitation; motor skill; tDCS
9.  Correspondence of electroencephalography and near-infrared spectroscopy sensitivities to the cerebral cortex using a high-density layout 
Neurophotonics  2014;1(2):025001-.
This study investigates the correspondence of the cortical sensitivity of electroencephalography (EEG) and near-infrared spectroscopy (NIRS). EEG forward model sensitivity to the cerebral cortex was calculated for 329 EEG electrodes following the 10-5 EEG positioning system using a segmented structural magnetic resonance imaging scan of a human subject. NIRS forward model sensitivity was calculated for the same subject using 156 NIRS source-detector pairs selected from 32 source and 32 detector optodes positioned on the scalp using a subset of the 10-5 EEG positioning system. Sensitivity correlations between colocalized NIRS source-detector pair groups and EEG channels yielded R = 0.46 ± 0.08. Groups of NIRS source-detector pairs with maximum correlations to EEG electrode sensitivities are tabulated. The mean correlation between the point spread functions for EEG and NIRS regions of interest (ROI) was R = 0.43 ± 0.07. Spherical ROIs with radii of 26 mm yielded the maximum correlation between EEG and NIRS averaged across all cortical mesh nodes. These sensitivity correlations between EEG and NIRS should be taken into account when designing multimodal studies of neurovascular coupling and when using NIRS as a statistical prior for EEG source localization.
doi:10.1117/1.NPh.1.2.025001
PMCID: PMC4280681  PMID: 25558462
electroencephalography; near-infrared spectroscopy; diffuse optical tomography; forward model; inverse model; sensitivity
10.  The sinonasal communication in the horse: examinations using computerized three-dimensional reformatted renderings of computed-tomography datasets 
Background
Sinusitis is a common disease in the horse. In human medicine it is described, that obstruction of the sinonasal communication plays a major role in the development of sinusitis. To get spatial sense of the equine specific communication ways between the nasal cavity and the paranasal sinuses, heads of 19 horses, aged 2 to 26 years, were analyzed using three-dimensional (3D) reformatted renderings of CT-datasets. Three-dimensional models were generated following manual and semi-automated segmentation. Before segmentation, the two-dimensional (2D) CT-images were verified against corresponding frozen sections of cadaveric heads.
Results
Three-dimensional analysis of the paranasal sinuses showed the bilateral existence of seven sinus compartments: rostral maxillary sinus, ventral conchal sinus, caudal maxillary sinus, dorsal conchal sinus, frontal sinus, sphenopalatine sinus and middle conchal sinus. The maxillary septum divides these seven compartments into two sinus systems: a rostral paranasal sinus system composed of the rostral maxillary sinus and the ventral conchal sinus and a caudal paranasal sinus system which comprises all other sinuses. The generated 3D models revealed a typically configuration of the sinonasal communication ways. The sinonasal communication started within the middle nasal meatus at the nasomaxillary aperture (Apertura nasomaxillaris), which opens in a common sinonasal channel (Canalis sinunasalis communis). This common sinonasal channel ramifies into a rostral sinonasal channel (Canalis sinunasalis rostralis) and a caudo-lateral sinonasal channel (Canalis sinunasalis caudalis). The rostral sinonasal channel ventilated the rostral paranasal sinus system, the caudo-lateral sinonasal channel opened into the caudal paranasal sinus system. The rostral sinonasal channel was connected to the rostral paranasal sinuses in various ways. Whereas, the caudal channel showed less anatomical variations and was in all cases connected to the caudal maxillary sinus. Volumetric measurements of the sinonasal channels showed no statistically significant differences (P <0.05) between the right and left side of the head.
Conclusions
Under physiologic conditions both paranasal sinus systems are connected to the nasal cavity by equine specific sinonasal channels. To resolve sinus disease it is aimed to maintain or even reconstruct the normal anatomy of the sinonasal communication by surgical intervention. Therefore, the presented 3D analyses may provide a useful basis.
doi:10.1186/1746-6148-10-72
PMCID: PMC3995307  PMID: 24646003
Horse; Computed tomography; Nasomaxillary aperture; Apertura nasomaxillaris; Upper airway; Sinonasal channel system; Paranasal sinuses
11.  Intra- and extra-cranial effects of transient blood pressure changes on brain near-infrared spectroscopy (NIRS) measurements 
Journal of Neuroscience Methods  2011;197(2):283-288.
Highlights
► We recorded NIRS from the visual cortex during pattern-reversal stimulation. ► Transient blood pressure changes were induced by arm-raising. ► Blood pressure changes significantly altered deep and shallow NIRS recordings. ► The effect appears to originate from both intra- and extra-cranial regions. ► Blood pressure must be considered as a potential confound in NIRS studies.
Brain near-infrared spectroscopy (NIRS) is an emerging neurophysiological tool that combines straightforward activity localization with cost–economy, portability and patient compatibility. NIRS is proving its empirical utility across specific cognitive and emotional paradigms. However, a potential limitation is that it is not only sensitive to haemodynamic changes taking place in the cortex, and task-related cardiovascular responses expressed in the perfusion of extracranial layers may be confounding. Existing literature reports correlations between brain NIRS and systemic blood pressure, yet it falls short of establishing whether in normal participants the blood pressure changes encountered in experimental settings can have confounding effects. Here, we tested this hypothesis by performing two experimental manipulations while recording from superficial occipital cortex, encompassing striate and extrastriate regions. Visual stimulation with reversing chequerboards evoked cortical haemodynamic responses. Simultaneously and independently, transient systemic blood pressure changes were generated through rapid arm-raising. Shallow-penetration NIRS recordings, probing only extra-cerebral tissues, highlighted close haemodynamic coupling with blood pressure. A different coupling pattern was observed in deep-penetration recordings directed at haemodynamic signals from visual cortex. In absence of blood-pressure changes, NIRS signals tracked differences in visual stimulus duration. However when blood pressure was actively manipulated, this effect was absent and replaced by a very large pressure-related response. Our observations demonstrate that blood pressure fluctuations can exert confounding effects on brain NIRS, through expression in extracranial tissues and within the brain itself. We highlight the necessity for continuous blood pressure monitoring alongside brain NIRS, and for further research on methods to correct for physiological confounds.
doi:10.1016/j.jneumeth.2011.02.029
PMCID: PMC3089735  PMID: 21392529
Near-infrared spectroscopy (NIRS); Blood pressure; Autonomic arousal; Visual stimulation
12.  Further improvement in reducing superficial contamination in NIRS using double short separation measurements 
NeuroImage  2013;85(0 1):10.1016/j.neuroimage.2013.01.073.
Near-Infrared Spectroscopy (NIRS) allows the recovery of the evoked hemodynamic response to brain activation. In adult human populations, the NIRS signal is strongly contaminated by systemic interference occurring in the superficial layers of the head. An approach to overcome this difficulty is to use additional NIRS measurements with short optode separations to measure the systemic hemodynamic fluctuations occurring in the superficial layers. These measurements can then be used as regressors in the post-experiment analysis to remove the systemic contamination and isolate the brain signal. In our previous work, we showed that the systemic interference measured in NIRS is heterogeneous across the surface of the scalp. As a consequence, the short separation measurement used in the regression procedure must be located close to the standard NIRS channel from which the evoked hemodynamic response of the brain is to be recovered. Here, we demonstrate that using two short separation measurements, one at the source optode and one at the detector optode, further increases the performance of the short separation regression method compared to using a single short separation measurement. While a single short separation channel produces an average reduction in noise of 33% for HbO, using a short separation channel at both source and detector reduces noise by 59% compared to the standard method using a general linear model (GLM) without short separation. For HbR, noise reduction of 3% is achieved using a single short separation and this number goes to 47% when two short separations are used. Our work emphasizes the importance of integrating short separation measurements both at the source and at the detector optode of the standard channels from which the hemodynamic response is to be recovered. While the implementation of short separation sources presents some difficulties experimentally, the improvement in noise reduction is significant enough to justify the practical challenges.
doi:10.1016/j.neuroimage.2013.01.073
PMCID: PMC3665655  PMID: 23403181
Near-Infrared Spectroscopy; Systemic Interference; Short Optode Separations; Kalman filtering; State-Space analysis
13.  Quantification of the cortical contribution to the NIRS signal over the motor cortex using concurrent NIRS-fMRI measurements 
Neuroimage  2011;59(4):3933-3940.
Near-Infrared Spectroscopy (NIRS) measures the functional hemodynamic response occuring at the surface of the cortex. Large pial veins are located above the surface of the cerebral cortex. Following activation, these veins exhibit oxygenation changes but their volume likely stays constant. The back-reflection geometry of the NIRS measurement renders the signal very sensitive to these superficial pial veins. As such, the measured NIRS signal contains contributions from both the cortical region as well as the pial vasculature. In this work, the cortical contribution to the NIRS signal was investigated using (1) Monte Carlo simulations over a realistic geometry constructed from anatomical and vascular MRI and (2) multimodal NIRS-BOLD recordings during motor stimulation. A good agreement was found between the simulations and the modeling analysis of in vivo measurements. Our results suggest that the cortical contribution to the deoxyhemoglobin signal change (ΔHbR) is equal to 16–22% of the cortical contribution to the total hemoglobin signal change (ΔHbT). Similarly, the cortical contribution of the oxyhemoglobin signal change (ΔHbO) is equal to 73–79% of the cortical contribution to the ΔHbT signal. These results suggest that ΔHbT is far less sensitive to pial vein contamination and therefore, it is likely that the ΔHbT signal provides better spatial specificity and should be used instead of ΔHbO or ΔHbR to map cerebral activity with NIRS. While different stimuli will result in different pial vein contributions, our finger tapping results do reveal the importance of considering the pial contribution.
doi:10.1016/j.neuroimage.2011.10.054
PMCID: PMC3279595  PMID: 22036999
NIRS-fMRI; Pial vasculature; Balloon Model; Monte Carlo simulations
14.  Experimental investigation of NIRS spatial sensitivity 
Biomedical Optics Express  2011;2(6):1478-1493.
Near infrared spectroscopy (NIRS) is regarded as a potential medical diagnostic technique for investigation of hemodynamic changes. However, uncertainties pertaining to the origin of NIRS signals have hampered its clinical interpretation. The uncertainities in NIRS measurements especially in case of living tissues are due to lack of rigorous combined theoretical-experimental studies resulting in clear understanding of the origin of NIRS signals. For their reliable interpretation it is important to understand the relationship between spatial changes in optical properties and corresponding changes in the NIRS signal. We investigated spatial sensitivity of near infrared optical measurements using an experimental approach. It uses a liquid optical phantom as tissue equivalent, which is explored under robot-control by a small, approximately point like perturbation of desired optical properties, and a NIRS instrument for trans-illumination/reflection measurements. The experimentally obtained sensitivity has been analyzed and compared with numerical simulations. In preliminary experiments we investigated the influence of various optical properties of the medium and of source/detector distances on the spatial sensitivity distribution. The acquired sensitivity maps can be used to define characteristic parameters. As an example, we used a 25% threshold to define a penetration depth measure which provides values in good accordance with published ones. To the best of our knowledge this is the first experimental study of NIRS spatial sensitivity. The presented method will allow in depth experimental investigation of the influence of various conditions pertaining to medium such as optical properties of tissue (scattering and absorption) and of the source/detector configuration.
doi:10.1364/BOE.2.001478
PMCID: PMC3114217  PMID: 21698012
(120.3890) Medical optics instrumentation; (170.3660) Light propagation in tissues; (300.1030) Absorption
15.  Cytochrome c oxidase response to changes in cerebral oxygen delivery in the adult brain shows higher brain-specificity than haemoglobin☆ 
Neuroimage  2014;85(Pt 1):234-244.
The redox state of cerebral mitochondrial cytochrome c oxidase monitored with near-infrared spectroscopy (Δ[oxCCO]) is a signal with strong potential as a non-invasive, bedside biomarker of cerebral metabolic status. We hypothesised that the higher mitochondrial density of brain compared to skin and skull would lead to evidence of brain-specificity of the Δ[oxCCO] signal when measured with a multi-distance near-infrared spectroscopy (NIRS) system. Measurements of Δ[oxCCO] as well as of concentration changes in oxygenated (Δ[HbO2]) and deoxygenated haemoglobin (Δ[HHb]) were taken at multiple source-detector distances during systemic hypoxia and hypocapnia (decrease in cerebral oxygen delivery), and hyperoxia and hypercapnia (increase in cerebral oxygen delivery) from 15 adult healthy volunteers. Increasing source-detector spacing is associated with increasing light penetration depth and thus higher sensitivity to cerebral changes. An increase in Δ[oxCCO] was observed during the challenges that increased cerebral oxygen delivery and the opposite was observed when cerebral oxygen delivery decreased. A consistent pattern of statistically significant increasing amplitude of the Δ[oxCCO] response with increasing light penetration depth was observed in all four challenges, a behaviour that was distinctly different from that of the haemoglobin chromophores, which did not show this statistically significant depth gradient. This depth-dependence of the Δ[oxCCO] signal corroborates the notion of higher concentrations of CCO being present in cerebral tissue compared to extracranial components and highlights the value of NIRS-derived Δ[oxCCO] as a brain-specific signal of cerebral metabolism, superior in this aspect to haemoglobin.
Highlights
•NIRS was used to measure oxidised cytochrome c oxidase (Δ[oxCCO]) in healthy brain.•Δ[oxCCO] changed in the same direction as changes in cerebral oxygen delivery.•Magnitude of Δ[oxCCO] response increased with increasing light penetration depth.•Corresponding haemoglobin changes showed no dependence on light penetration depth.•NIRS-measured Δ[oxCCO] has higher brain specificity than haemoglobin.
doi:10.1016/j.neuroimage.2013.05.070
PMCID: PMC3898943  PMID: 23707584
Cytochrome c oxidase; Hypoxia; Hyperoxia; Hypocapnia; Hypercapnia; Near-infrared spectroscopy
16.  Functional near-infrared spectroscopy for the assessment of overt reading 
Brain and Behavior  2012;2(6):825-837.
Functional near-infrared spectroscopy (fNIRS) has become increasingly established as a promising technique for monitoring functional brain activity. To our knowledge, no study has yet used fNIRS to investigate overt reading of irregular words and nonwords with a full coverage of the cerebral regions involved in reading processes. The aim of our study was to design and validate a protocol using fNIRS for the assessment of overt reading. Twelve healthy French-speaking adults underwent one session of fNIRS recording while performing an overt reading of 13 blocks of irregular words and nonwords. Reading blocks were separated by baseline periods during which participants were instructed to fixate a cross. Sources (n = 55) and detectors (n = 16) were placed bilaterally over frontal, temporal, parietal, and occipital regions. Two wavelengths were used: 690 nm, more sensitive to deoxyhemoglobin (HbR) concentration changes, and 830 nm, more sensitive to oxyhemoglobin (HbO) concentration changes. For all participants, total hemoglobin (HbT) concentrations (HbO + HbR) were significantly higher than baseline for both irregular word and nonword reading in the inferior frontal gyri, the middle and superior temporal gyri, and the occipital cortices bilaterally. In the temporal gyri, although the difference was not significant, [HbT] values were higher in the left hemisphere. In the bilateral inferior frontal gyri, higher [HbT] values were found in nonword than in irregular word reading. This activation could be related to the grapheme-to-phoneme conversion characterizing the phonological pathway of reading. Our findings confirm that fNIRS is an appropriate technique to assess the neural correlates of overt reading.
doi:10.1002/brb3.100
PMCID: PMC3500469  PMID: 23170245
Adults; irregular words; lexical reading; nonwords; optical imaging; phonological reading; reading aloud
17.  Accuracy of oxygen saturation and total hemoglobin estimates in the neonatal brain using the semi-infinite slab model for FD-NIRS data analysis 
Biomedical Optics Express  2014;5(12):4300-4312.
Frequency domain near-infrared spectroscopy (FD-NIRS) is a non-invasive method for measuring optical absorption in the brain. Common data analysis procedures for FD-NIRS data assume the head is a semi-infinite, homogenous medium. This assumption introduces bias in estimates of absorption (μa), scattering ( μs′), tissue oxygen saturation (StO2), and total hemoglobin (HbT). Previous works have investigated the accuracy of recovered μa values under this assumption. The purpose of this study was to examine the accuracy of recovered StO2 and HbT values in FD-NIRS measurements of the neonatal brain. We used Monte Carlo methods to compute light propagation through a neonate head model in order to simulate FD-NIRS measurements at 690 nm and 830 nm. We recovered μa, μs′, StO2, and HbT using common analysis procedures that assume a semi-infinite, homogenous medium and compared the recovered values to simulated values. Additionally, we characterized the effects of curvature via simulations on homogenous spheres of varying radius. Lastly, we investigated the effects of varying amounts of extra-axial fluid. Curvature induced underestimation of μa, μs′, and HbT, but had minimal effects on StO2. For the morphologically normal neonate head model, the mean absolute percent errors (MAPE) of recovered μa values were 12% and 7% for 690 nm and 830 nm, respectively, when source-detector separation was at least 20 mm. The MAPE for recovered StO2 and HbT were 6% and 9%, respectively. Larger relative errors were observed (∼20–30%), especially as StO2 and HbT deviated from normal values. Excess CSF around the brain caused very large errors in μa, μs′, and HbT, but had little effect on StO2.
doi:10.1364/BOE.5.004300
PMCID: PMC4285606  PMID: 25574439
(170.3660) Light propagation in tissues; (170.5380) Physiology; (300.0300) Spectroscopy
18.  Sensitivity of near-infrared spectroscopy and diffuse correlation spectroscopy to brain hemodynamics: simulations and experimental findings during hypercapnia 
Neurophotonics  2014;1(1):015005.
Abstract.
Near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) are two diffuse optical technologies for brain imaging that are sensitive to changes in hemoglobin concentrations and blood flow, respectively. Measurements for both modalities are acquired on the scalp, and therefore hemodynamic processes in the extracerebral vasculature confound the interpretation of cortical hemodynamic signals. The sensitivity of NIRS to the brain versus the extracerebral tissue and the contrast-to-noise ratio (CNR) of NIRS to cerebral hemodynamic responses have been well characterized, but the same has not been evaluated for DCS. This is important to assess in order to understand their relative capabilities in measuring cerebral physiological changes. We present Monte Carlo simulations on a head model that demonstrate that the relative brain-to-scalp sensitivity is about three times higher for DCS (0.3 at 3 cm) than for NIRS (0.1 at 3 cm). However, because DCS has higher levels of noise due to photon-counting detection, the CNR is similar for both modalities in response to a physiologically realistic simulation of brain activation. Even so, we also observed higher CNR of the hemodynamic response during graded hypercapnia in adult subjects with DCS than with NIRS.
doi:10.1117/1.NPh.1.1.015005
PMCID: PMC4247161  PMID: 25453036
near-infrared spectroscopy; diffuse correlation spectroscopy; functional brain imaging; hypercapnia
19.  Brain Specificity of Diffuse Optical Imaging: Improvements from Superficial Signal Regression and Tomography 
Functional near infrared spectroscopy (fNIRS) is a portable monitor of cerebral hemodynamics with wide clinical potential. However, in fNIRS, the vascular signal from the brain is often obscured by vascular signals present in the scalp and skull. In this paper, we evaluate two methods for improving in vivo data from adult human subjects through the use of high-density diffuse optical tomography (DOT). First, we test whether we can extend superficial regression methods (which utilize the multiple source–detector pair separations) from sparse optode arrays to application with DOT imaging arrays. In order to accomplish this goal, we modify the method to remove physiological artifacts from deeper sampling channels using an average of shallow measurements. Second, DOT provides three-dimensional image reconstructions and should explicitly separate different tissue layers. We test whether DOT's depth-sectioning can completely remove superficial physiological artifacts. Herein, we assess improvements in signal quality and reproducibility due to these methods using a well-characterized visual paradigm and our high-density DOT system. Both approaches remove noise from the data, resulting in cleaner imaging and more consistent hemodynamic responses. Additionally, the two methods act synergistically, with greater improvements when the approaches are used together.
doi:10.3389/fnene.2010.00014
PMCID: PMC2914577  PMID: 20725524
neuroimaging; biomedical optics; near-infrared spectroscopy; diffuse optical tomography; artifact removal; image quality
20.  Intraoperative Transillumination to Determine the Extent of Frontal Sinus in Subcranial Approach to Anterior Skull Base 
Skull Base  2011;21(2):71-74.
We sought to determine the extent of the frontal sinus by intraoperative transillumination through the superomedial orbital wall in a subcranial approach to the anterior skull base. After raising a bicoronal flap, the frontal sinus was transilluminated through the superomedial orbital wall with a fiber-optic light source, delineating the extent of the frontal sinus. The frontal sinus boundary was marked with a marker pen. A frontal sinus anterior wall osteotomy was performed with a sagittal saw, staying within the confines of the frontal sinus marking. A bone flap was removed, and the posterior wall was drilled out. The remaining procedure was performed in a standard fashion. At the end of the procedure, the bone flap was fixed with a titanium plate. A total of 58 patients had undergone craniofacial resection from January 2004 to December 2007. In 13 patients, a subcranial approach was employed using the transillumination technique. Transillumination was successful in delineating the frontal sinus periphery in all 13 patients. Intraoperative transillumination of the frontal sinus through the superomedial orbital wall is a simple and effective method to delineate the frontal sinus periphery in a subcranial approach to the anterior skull base.
doi:10.1055/s-0030-1261267
PMCID: PMC3312596  PMID: 22451803
Transillumination of frontal sinus; subcranial approach; frontal craniotomy; osteoplastic flap; anterior skull base
21.  Origins of Spatial Working Memory Deficits in Schizophrenia: An Event-Related fMRI and Near-Infrared Spectroscopy Study 
PLoS ONE  2008;3(3):e1760.
Abnormal prefrontal functioning plays a central role in the working memory (WM) deficits of schizophrenic patients, but the nature of the relationship between WM and prefrontal activation remains undetermined. Using two functional neuroimaging methods, we investigated the neural correlates of remembering and forgetting in schizophrenic and healthy participants. We focused on the brain activation during WM maintenance phase with event-related functional magnetic resonance imaging (fMRI). We also examined oxygenated hemoglobin changes in relation to memory performance with the near-infrared spectroscopy (NIRS) using the same spatial WM task. Distinct types of correct and error trials were segregated for analysis. fMRI data indicated that prefrontal activation was increased during WM maintenance on correct trials in both schizophrenic and healthy subjects. However, a significant difference was observed in the functional asymmetry of frontal activation pattern. Healthy subjects showed increased activation in the right frontal, temporal and cingulate regions. Schizophrenic patients showed greater activation compared with control subjects in left frontal, temporal and parietal regions as well as in right frontal regions. We also observed increased ‘false memory’ errors in schizophrenic patients, associated with increased prefrontal activation and resembling the activation pattern observed on the correct trials. NIRS data replicated the fMRI results. Thus, increased frontal activity was correlated with the accuracy of WM in both healthy control and schizophrenic participants. The major difference between the two groups concerned functional asymmetry; healthy subjects recruited right frontal regions during spatial WM maintenance whereas schizophrenic subjects recruited a wider network in both hemispheres to achieve the same level of memory performance. Increased “false memory” errors and accompanying bilateral prefrontal activation in schizophrenia suggest that the etiology of memory errors must be considered when comparing group performances. Finally, the concordance of fMRI and NIRS data supports NIRS as an alternative functional neuroimaging method for psychiatric research.
doi:10.1371/journal.pone.0001760
PMCID: PMC2257999  PMID: 18335036
22.  Assessment of frontal sinus dimensions to determine sexual dimorphism among Indian adults 
Background:
Sex identification of unknown individuals is important in forensic sciences. At times when only skull remains are found and other means of identification fails, radiographs of frontal sinus can be used for identification. Frontal sinus morphology is unique to individual and can be used effectively in person identification; whereas its use in determining sexual dimorphism is limited.
Aim:
To determine sexual dimorphism among Indians by evaluating frontal sinus pattern using postero-anterior radiograph.
Materials and Methods:
The right and left areas, maximum height and width of frontal sinus were determined in 300 digital postero-anterior view radiographs obtained from 150 males and 150 females aged between 18-30 years. The measurements were carried out by transferring the image to Adobe® Photoshop® CS3 extended. Comparison of values were done using student's t-test and accuracy of sex determination was assessed through Logistic regression analysis.
Results and Conclusions:
One hundred and forty seven males and 142 females show presence of frontal sinus with seven individuals showing unilateral/bilateral absence of frontal sinuses. The mean values of the frontal sinus height, width and area are greater in males. Right frontal sinus is larger than the left sinus in both the sex. The mathematical model based on logistic regression analysis gives an average concordance index for sex determination of 64.6%. Thus, frontal sinus provides average accuracy in sex determination among Indian population. This may be due to its greater variation in morphology.
doi:10.4103/0975-1475.127766
PMCID: PMC3970383  PMID: 24695810
Frontal sinus; forensic identification; human skull; sex determination
23.  Near-infrared spectroscopy measurement of the pulsatile component of cerebral blood flow and volume from arterial oscillations 
Journal of biomedical optics  2007;12(1):014033.
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.
doi:10.1117/1.2710250
PMCID: PMC2637815  PMID: 17343508
cerebral blood flow; cerebral blood volume; near-infrared spectroscopy; arterial oscillations
24.  The Utility of Near Infrared Spectroscopy in Detecting Intracranial Hemorrhage in Children 
Journal of Neurotrauma  2012;29(6):1047-1053.
Abstract
A prospective case-control study was conducted in a tertiary care pediatric intensive care unit (PICU) to evaluate the use of near infrared spectroscopy (NIRS) for the detection of intracranial hemorrhage (ICH) in children. Subjects 0–14 years of age who had a computed tomography (CT) scan of the head performed as part of clinical care were eligible for enrollment. The children were stratified into two groups based on whether the CT was normal or abnormal. Children in the abnormal imaging cohort were further divided into those with ICH and those with other abnormalities of the brain parenchyma (contusions, diffuse axonal injury [DAI], or cerebral edema) or fractures. NIRS measurements were performed on all subjects within 24 h of head CT. The NIRS operator was blinded to the presence or absence of ICH. NIRS measurements were performed in eight different scalp locations (four bilaterally). A total of 103 measurements were made. The optical density (OD) was automatically calculated by comparing the reflected and diffused optical signal. A ΔOD>0.2 between hemispheres in any scalp location was considered abnormal. NIRS was performed in a total of 28 subjects: 7 had normal imaging and 21 had abnormal imaging. Of those with abnormal imaging, 12 had ICH. The sensitivity and specificity of NIRS at detecting ICH was 1.0 and 0.8, respectively. The positive and negative predictive values were 0.8 and 1.0, respectively. In conclusion, NIRS correctly identified all cases of ICH in this pilot study. Our preliminary results suggest that NIRS may be beneficial in the evaluation of a child with possible ICH.
doi:10.1089/neu.2011.1890
PMCID: PMC3325547  PMID: 22098538
abusive head trauma; children; intracranial hemorrhage; near infrared spectroscopy; traumatic brain injury
25.  Validating a new methodology for optical probe design and image registration in fNIRS studies 
NeuroImage  2015;106:86-100.
Functional near-infrared spectroscopy (fNIRS) is an imaging technique that relies on the principle of shining near-infrared light through tissue to detect changes in hemodynamic activation. An important methodological issue encountered is the creation of optimized probe geometry for fNIRS recordings. Here, across three experiments, we describe and validate a processing pipeline designed to create an optimized, yet scalable probe geometry based on selected regions of interest (ROIs) from the functional magnetic resonance imaging (fMRI) literature. In experiment 1, we created a probe geometry optimized to record changes in activation from target ROIs important for visual working memory. Positions of the sources and detectors of the probe geometry on an adult head were digitized using a motion sensor and projected onto a generic adult atlas and a segmented head obtained from the subject's MRI scan. In experiment 2, the same probe geometry was scaled down to fit a child's head and later digitized and projected onto the generic adult atlas and a segmented volume obtained from the child's MRI scan. Using visualization tools and by quantifying the amount of intersection between target ROIs and channels, we show that out of 21 ROIs, 17 and 19 ROIs intersected with fNIRS channels from the adult and child probe geometries, respectively. Further, both the adult atlas and adult subject-specific MRI approaches yielded similar results and can be used interchangeably. However, results suggest that segmented heads obtained from MRI scans be used for registering children's data. Finally, in experiment 3, we further validated our processing pipeline by creating a different probe geometry designed to record from target ROIs involved in language and motor processing.
PMCID: PMC4431570  PMID: 25705757
Functional near infrared spectroscopy; Probe geometry; Optode co-registration; Visual working memory; AtlasViewerGUI

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