Near-infrared spectroscopy (NIRS) is a noninvasive neuroimaging tool for studying evoked hemodynamic changes within the brain. By this technique, changes in the optical absorption of light are recorded over time and are used to estimate the functionally evoked changes in cerebral oxyhemoglobin and deoxyhemoglobin concentrations that result from local cerebral vascular and oxygen metabolic effects during brain activity. Over the past three decades this technology has continued to grow, and today NIRS studies have found many niche applications in the fields of psychology, physiology, and cerebral pathology. The growing popularity of this technique is in part associated with a lower cost and increased portability of NIRS equipment when compared with other imaging modalities, such as functional magnetic resonance imaging and positron emission tomography. With this increasing number of applications, new techniques for the processing, analysis, and interpretation of NIRS data are continually being developed. We review some of the time-series and functional analysis techniques that are currently used in NIRS studies, we describe the practical implementation of various signal processing techniques for removing physiological, instrumental, and motion-artifact noise from optical data, and we discuss the unique aspects of NIRS analysis in comparison with other brain imaging modalities. These methods are described within the context of the MATLAB-based graphical user interface program, HomER, which we have developed and distributed to facilitate the processing of optical functional brain data.

Near-infrared spectroscopy (NIRS) and diffuse optical imaging (DOI) are finding widespread application in the study of human brain activation, motivating further application-specific development of the technology. NIRS and DOI offer the potential to quantify changes in deoxyhemoglobin (HbR) and total hemoglobin (HbT) concentration, thus enabling distinction of oxygen consumption and blood flow changes during brain activation. While the techniques implemented presently provide important results for cognition and the neurosciences through their relative measures of HbR and HbT concentrations, there is much to be done to improve sensitivity, accuracy, and resolution. In this paper, we review the advances currently being made and issues to consider for improving optical image quality. These include the optimal selection of wavelengths to minimize random and systematic error propagation in the calculation of the hemoglobin concentrations, the filtering of systemic physiological signal clutter to improve sensitivity to the hemodynamic response to brain activation, the implementation of overlapping measurements to improve image spatial resolution and uniformity, and the utilization of spatial prior information from structural and functional MRI to reduce DOI partial volume error and improve image quantitative accuracy. D 2004 Elsevier Inc. All rights reserved.

In this study, we have preformed simultaneous near-infrared spectroscopy (NIRS) along with BOLD (blood oxygen level dependent) and ASL (arterial spin labeling)-based fMRI during an event-related motor activity in human subjects in order to compare the temporal dynamics of the hemodynamic responses recorded in each method. These measurements have allowed us to examine the validity of the biophysical models underlying each modality and, as a result, gain greater insight into the hemodynamic responses to neuronal activation. Although prior studies have examined the relationships between these two methodologies through similar experiments, they have produced conflicting results in the literature for a variety of reasons. Here, by employing a short-duration, event-related motor task, we have been able to emphasize the subtle temporal differences between the hemodynamic parameters with a high contrast-to-noise ratio. As a result of this improved experimental design, we are able to report that the fMRI measured BOLD response is more correlated with the NIRS measure of deoxy-hemoglobin (R = 0.98; P < 10(-20)) than with oxy-hemoglobin (R = 0.71), or total hemoglobin (R = 0.53). This result was predicted from the theoretical grounds of the BOLD response and is in agreement with several previous works [Toronov, V.A.W., Choi, J.H., Wolf, M., Michalos, A., Gratton, E., Hueber, D., 2001. "Investigation of human brain hemodynamics by simultaneous near-infrared spectroscopy and functional magnetic resonance imaging." Med. Phys. 28 (4) 521-527.; MacIntosh, B.J., Klassen, L.M., Menon, R.S., 2003. "Transient hemodynamics during a breath hold challenge in a two part functional imaging study with simultaneous near-infrared spectroscopy in adult humans". NeuroImage 20 1246-1252.; Toronov, V.A.W., Walker, S., Gupta, R., Choi, J.H., Gratton, E., Hueber, D., Webb, A., 2003. "The roles of changes in deoxyhemoglobin concentration and regional cerebral blood volume in the fMRI BOLD signal" Neuroimage 19 (4) 1521-1531]. These data have also allowed us to examine more detailed measurement models of the fMRI signal and comment on the roles of the oxygen saturation and blood volume contributions to the BOLD response. In addition, we found high correlation between the NIRS measured total hemoglobin and ASL measured cerebral blood flow (R = 0.91; P < 10(-10)) and oxy-hemoglobin with flow (R = 0.83; P < 10(-05)) as predicted by the biophysical models. Finally, we note a significant amount of cross-modality, correlated, inter-subject variability in amplitude change and time-to-peak of the hemodynamic response. The observed co-variance in these parameters between subjects is in agreement with hemodynamic models and provides further support that fMRI and NIRS have similar vascular sensitivity.

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Diffuse optical imaging is an effective technique for noninvasive functional brain imaging. However, the measurements respond to systemic hemodynamic fluctuations caused by the cardiac cycle, respiration, and blood pressure, which may obscure or overwhelm the desired stimulus-evoked response. Previous work on this problem employed temporal filtering, estimation of systemic effects from background pixels, or modeling of interference signals with predefined basis functions, with some success. However, weak signals are still lost in the interference, and other complementary methods are desirable. We use the spatial behavior of measured baseline signals to identify the interference subspaces. We then project signals components in this subspace out of the stimulation data. In doing so, we assume that systemic interference components will be more global spatially, with higher energy, than the stimulus-evoked signals of interest. Thus, the eigenvectors corresponding to the largest eigenvalues of an appropriate correlation matrix form the basis for an interference subspace. By projecting the data onto the orthogonal nullspace of these eigenvectors, we can obtain more localized response, as reflected in improved contrast-to-noise ratio and correlation coefficient maps.

We have performed a noninvasive bilateral optical imaging study of the hemodynamic evoked response to unilateral finger opposition task, finger tactile, and electrical median nerve stimulation in the human sensorimotor cortex. This optical study shows the hemoglobin-evoked response to voluntary and nonvoluntary stimuli. We performed measurements on 10 healthy volunteers using block paradigms for motor, sensory, and electrical stimulations of the right and left hands separately. We analyzed the spatial/temporal features and the amplitude of the optical signal induced by cerebral activation during these three paradigms. We consistently found an increase (decrease) in the cerebral concentration of oxy-hemoglobin (deoxy-hemoglobin) at the cortical side contralateral to the stimulated side. We observed an optical response to activation that was larger in size and amplitude during voluntary motor task compared to the other two stimulations. The ipsilateral response was consistently smaller than the contralateral response, and even reversed (i.e., a decrease in oxy-hemoglobin, and an increase in deoxy-hemoglobin) in the case of the electrical stimulation. We observed a systemic contribution to the optical signal from the increase in the heart rate increase during stimulation, and we made a first attempt to subtract it from the evoked hemoglobin signal. Our findings based on optical imaging are in agreement with results in the literature obtained with positron emission tomography and functional magnetic resonance imaging.

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Abstract.We have used continuous-wave (CW) and frequency-domain spectroscopy to investigate the optical properties of the newborn piglet brain in vivo and non-invasively. Three anaesthetized, intubated, ventilated and instrumented newborn piglets were placed into a stereotaxic instrument for optimal experimental stability, reproducible probe-to-scalp optical contact and 3D adjustment of the optical probe. By measuring the absolute values of the brain absorption and reduced scattering coefficients at two wavelengths (758 and 830 nm), frequency-domain spectroscopy provided absolute readings (in contrast to the relative readings of CW spectroscopy) of cerebral haemoglobin concentration and saturation during experimentally induced perturbations in cerebral haemodynamics and oxygenation. Such perturbations included a modulation of the inspired oxygen concentration, transient brain asphyxia, carotid artery occlusion and terminal brain asphyxia. The baseline cerebral haemoglobin saturation and concentration, measured with frequency-domain spectroscopy, were about 60% and 42 μM respectively. The cerebral saturation values ranged from a minimum of 17% (during transient brain asphyxia) to a maximum of 80% (during recovery from transient brain asphyxia). To analyse the CW optical data, we have (a) derived a mathematical relationship between the cerebral optical properties and the differential pathlength factor and (b) introduced a method based on the spatial dependence of the detected intensity (dc slope method). The analysis of the cerebral optical signals associated with the arterial pulse and with respiration demonstrates that motion artefacts can significantly affect the intensity recorded from a single optode pair. Motion artefacts can be strongly reduced by combining data from multiple optodes to provide relative readings in the dc slope method. We also report significant biphasic changes (initial decrease and successive increase) in the reduced scattering coefficient measured in the brain after the piglet had been sacrificed.