Meryem A. Yücel

Short separation channel location impacts the performance of short channel regression in NIRS

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.

Quantification of the cortical contribution to the NIRS signal over the motor cortex using concurrent NIRS-fMRI measurements.

Near-Infrared Spectroscopy (NIRS) measures the functional hemodynamic response occurring 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.

Further improvement in reducing superficial contamination in NIRS using double short separation measurements

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.

Large arteriolar component of oxygen delivery implies a safe margin of oxygen supply to cerebral tissue

What is the organization of cerebral microvascular oxygenation and morphology that allows adequate tissue oxygenation at different activity levels? We address this question in the mouse cerebral cortex using microscopic imaging of intravascular O2 partial pressure and blood flow combined with numerical modeling. Here we show that parenchymal arterioles are responsible for 50% of the extracted O2 at baseline activity and the majority of the remaining O2 exchange takes place within the first few capillary branches. Most capillaries release little O2 at baseline acting as an O2 reserve that is recruited during increased neuronal activity or decreased blood flow. Our results challenge the common perception that capillaries are the major site of O2 delivery to cerebral tissue. The understanding of oxygenation distribution along arterio-capillary paths may have profound implications for the interpretation of BOLD fMRI signal and for evaluating microvascular O2 delivery capacity to support cerebral tissue in disease.

Quantifying the Microvascular Origin of BOLD-fMRI from First Principles with Two-Photon Microscopy and an Oxygen-Sensitive Nanoprobe

The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes in blood volume and oxygenation rather than neuronal activity per se. Therefore, understanding the transformation of microscopic vascular behavior into macroscopic BOLD signals is at the foundation of physiologically informed noninvasive neuroimaging. Here, we use oxygen-sensitive two-photon microscopy to measure the BOLD-relevant microvascular physiology occurring within a typical rodent fMRI voxel and predict the BOLD signal from first principles using those measurements. The predictive power of the approach is illustrated by quantifying variations in the BOLD signal induced by the morphological folding of the human cortex. This framework is then used to quantify the contribution of individual vascular compartments and other factors to the BOLD signal for different magnet strengths and pulse sequences.

Anatomical guidance for functional near-infrared spectroscopy: AtlasViewer tutorial

Abstract. Functional near-infrared spectroscopy (fNIRS) is an optical imaging method that is used to noninvasively measure cerebral hemoglobin concentration changes induced by brain activation. Using structural guidance in fNIRS research enhances interpretation of results and facilitates making comparisons between studies. AtlasViewer is an open-source software package we have developed that incorporates multiple spatial registration tools to enable structural guidance in the interpretation of fNIRS studies. We introduce the reader to the layout of the AtlasViewer graphical user interface, the folder structure, and user files required in the creation of fNIRS probes containing sources and detectors registered to desired locations on the head, evaluating probe fabrication error and intersubject probe placement variability, and different procedures for estimating measurement sensitivity to different brain regions as well as image reconstruction performance. Further, we detail how AtlasViewer provides a generic head atlas for guiding interpretation of fNIRS results, but also permits users to provide subject-specific head anatomies to interpret their results. We anticipate that AtlasViewer will be a valuable tool in improving the anatomical interpretation of fNIRS studies.

Specificity of Hemodynamic Brain Responses to Painful Stimuli: A functional near-infrared spectroscopy study

Assessing pain in individuals not able to communicate (e.g. infants, under surgery, or following stroke) is difficult due to the lack of non-verbal objective measures of pain. Near-infrared spectroscopy (NIRS) being a portable, non-invasive and inexpensive method of monitoring cerebral hemodynamic activity has the potential to provide such a measure. Here we used functional NIRS to evaluate brain activation to an innocuous and a noxious electrical stimulus on healthy human subjects (n = 11). For both innocuous and noxious stimuli, we observed a signal change in the primary somatosensory cortex contralateral to the stimulus. The painful and non-painful stimuli can be differentiated based on their signal size and profile. We also observed that repetitive noxious stimuli resulted in adaptation of the signal. Furthermore, the signal was distinguishable from a skin sympathetic response to pain that tended to mask it. Our results support the notion that functional NIRS has a potential utility as an objective measure of pain.

Reducing motion artifacts for long-term clinical NIRS monitoring using collodion-fixed prism-based optical fibers.

As the applications of near-infrared spectroscopy (NIRS) continue to broaden and long-term clinical monitoring becomes more common, minimizing signal artifacts due to patient movement becomes more pressing. This is particularly true in applications where clinically and physiologically interesting events are intrinsically linked to patient movement, as is the case in the study of epileptic seizures. In this study, we apply an approach common in the application of EEG electrodes to the application of specialized NIRS optical fibers. The method provides improved optode-scalp coupling through the use of miniaturized optical fiber tips fixed to the scalp using collodion, a clinical adhesive. We investigate and quantify the performance of this new method in minimizing motion artifacts in healthy subjects, and apply the technique to allow continuous NIRS monitoring throughout epileptic seizures in two epileptic in-patients. Using collodion-fixed fibers reduces the percent signal change of motion artifacts by 90% and increases the SNR by 6 and 3 fold at 690 and 830 nm wavelengths respectively when compared to a standard Velcro-based array of optical fibers. The SNR has also increased by 2 fold during rest conditions without motion with the new probe design because of better light coupling between the fiber and scalp. The change in both HbO and HbR during motion artifacts is found to be statistically lower for the collodion-fixed fiber probe. The collodion-fixed optical fiber approach has also allowed us to obtain good quality NIRS recording of three epileptic seizures in two patients despite excessive motion in each case.

TARGETED PRINCIPLE COMPONENT ANALYSIS: A NEW MOTION ARTIFACT CORRECTION APPROACH FOR NEAR-INFRARED SPECTROSCOPY

As near-infrared spectroscopy (NIRS) broadens its application area to different age and disease groups, motion artifacts in the NIRS signal due to subject movement is becoming an important challenge. Motion artifacts generally produce signal fluctuations that are larger than physiological NIRS signals, thus it is crucial to correct for them before obtaining an estimate of stimulus evoked hemodynamic responses. There are various methods for correction such as principle component analysis (PCA), wavelet-based filtering and spline interpolation. Here, we introduce a new approach to motion artifact correction, targeted principle component analysis (tPCA), which incorporates a PCA filter only on the segments of data identified as motion artifacts. It is expected that this will overcome the issues of filtering desired signals that plagues standard PCA filtering of entire data sets. We compared the new approach with the most effective motion artifact correction algorithms on a set of data acquired simultaneously with a collodion-fixed probe (low motion artifact content) and a standard Velcro probe (high motion artifact content). Our results show that tPCA gives statistically better results in recovering hemodynamic response function (HRF) as compared to wavelet-based filtering and spline interpolation for the Velcro probe. It results in a significant reduction in mean-squared error (MSE) and significant enhancement in Pearson’s correlation coefficient to the true HRF. The collodion-fixed fiber probe with no motion correction performed better than the Velcro probe corrected for motion artifacts in terms of MSE and Pearson’s correlation coefficient. Thus, if the experimental study permits, the use of a collodion-fixed fiber probe may be desirable. If the use of a collodion-fixed probe is not feasible, then we suggest the use of tPCA in the processing of motion artifact contaminated data.

Short separation regression improves statistical significance and better localizes the hemodynamic response obtained by near-infrared spectroscopy for tasks with differing autonomic responses

Abstract. Autonomic nervous system response is known to be highly task-dependent. The sensitivity of near-infrared spectroscopy (NIRS) measurements to superficial layers, particularly to the scalp, makes it highly susceptible to systemic physiological changes. Thus, one critical step in NIRS data processing is to remove the contribution of superficial layers to the NIRS signal and to obtain the actual brain response. This can be achieved using short separation channels that are sensitive only to the hemodynamics in the scalp. We investigated the contribution of hemodynamic fluctuations due to autonomous nervous system activation during various tasks. Our results provide clear demonstrations of the critical role of using short separation channels in NIRS measurements to disentangle differing autonomic responses from the brain activation signal of interest.