Special Section Guest Editorial: Thirty Years of Functional Near-Infrared Spectroscopy.

Functional Near-Infrared Spectroscopy (fNIRS) is a non-invasive optical technique that measures cerebral hemodynamics across multiple regions of interest, and thereby characterises brain functional activation. Since its first description in 1993, fNIRS has undergone substantial developments in hardware, analysis techniques, and applications. Thirty years later, this technique is significantly enchancing our understanding in diverse areas of neuroscience research such as neurodevelopment, cognitive neuroscience, psychiatric disorders, neurodegenerative conditions, and brain injury management in intensive care settings. This special issue outlines the latest progress in instrumentation and analysis techniques and showcases some applications within the expanding field of fNIRS over the past decade.

Optimizing a two-layer method for hybrid diffuse correlation spectroscopy and frequency-domain diffuse optical spectroscopy cerebral measurements in adults.

Significance: The sensitivity to extracerebral tissues is a well-known confounder of diffuse optics. Two-layer (2L) head models can separate cerebral signals from extracerebral artifacts, but they also carry the risk of crosstalk between fitting parameters. Aim: We aim to implement a constrained 2L head model for hybrid diffuse correlation spectroscopy (DCS) and frequency-domain diffuse optical spectroscopy (FD-DOS) data and to characterize errors in cerebral blood flow and tissue absorption with the proposed model. Approach: The algorithm uses the analytical solution of a 2L cylinder and an a priori extracerebral layer thickness to fit multidistance FD-DOS (0.8 to 4 cm) and DCS (0.8 and 2.5 cm) data, assuming homogeneous tissue reduced scattering. We characterized the algorithm's accuracy for simulated data with noise generated using a 2L slab and realistic adult head geometries and for in vitro phantom data. Results: Our algorithm recovered the cerebral flow index with 6.3 [2.8, 13.2]% and 34 [30, 42]% (median absolute percent error [interquartile range]) for slab and head geometries, respectively. Corresponding errors in the cerebral absorption coefficient were 5.0 [3.0, 7.9]% and 4.6 [2.4, 7.2]% for the slab and head geometries and 8 [5, 12]% for our phantom experiment. Our results were minimally sensitive to second-layer scattering changes and were robust to cross-talk between fitting parameters. Conclusions: In adults, the constrained 2L algorithm promises to improve FD-DOS/DCS accuracy compared with the conventional semi-infinite approach.

Revealing the spatiotemporal requirements for accurate subject identification with resting-state functional connectivity: a simultaneous fNIRS-fMRI study.

Significance: Brain fingerprinting refers to identifying participants based on their functional patterns. Despite its success with functional magnetic resonance imaging (fMRI), brain fingerprinting with functional near-infrared spectroscopy (fNIRS) still lacks adequate validation. Aim: We investigated how fNIRS-specific acquisition features (limited spatial information and nonneural contributions) influence resting-state functional connectivity (rsFC) patterns at the intra-subject level and, therefore, brain fingerprinting. Approach: We performed multiple simultaneous fNIRS and fMRI measurements in 29 healthy participants at rest. Data were preprocessed following the best practices, including the removal of motion artifacts and global physiology. The rsFC maps were extracted with the Pearson correlation coefficient. Brain fingerprinting was tested with pairwise metrics and a simple linear classifier. Results: Our results show that average classification accuracy with fNIRS ranges from 75% to 98%, depending on the number of runs and brain regions used for classification. Under the right conditions, brain fingerprinting with fNIRS is close to the 99.9% accuracy found with fMRI. Overall, the classification accuracy is more impacted by the number of runs and the spatial coverage than the choice of the classification algorithm. Conclusions: This work provides evidence that brain fingerprinting with fNIRS is robust and reliable for extracting unique individual features at the intra-subject level once relevant spatiotemporal constraints are correctly employed.

Can tactile reactivity in preterm born infants be explained by an immature cortical response to tactile stimulation in the first year? A pilot study.

This study aimed to compare preterm (PT) and full-term (FT) infants' adaptive behavior and functional cortical response to tactile stimulus, as measured by Test of Sensory Functions in Infants and functional Near-Infrared Spectroscopy (fNIRS). Outcome measures were taken at 6 (PT = 26/FT = 21 infants) and 12 months (PT = 15/FT = 14 infants). At 6 months, poorer tactile reactivity was observed in PT, but not confirmed at 12 months. At 6 months, cortical response to tactile stimulus was found in the primary sensorimotor cortex and differences between groups did not reach significance. At 12 months, cortical response was found in the primary sensorimotor cortex and premotor area and in the somatosensory associative area, with significant less frequent response in premotor area in PT. The findings reinforce fNIRS as a tool to complement the knowledge of tactile adaptive behaviors in PT in early life.

Quantification of the Tissue Oxygenation Delay Induced by Breath-Holding in Patients with Carotid Atherosclerosis.

Carotid artery stenosis (CAS) is a common vascular disease with long-term consequences for the brain. Although CAS is strongly associated with impaired cerebral hemodynamics and neurodegeneration, the mechanisms underlying hemodynamic impairment in the microvasculature remain unknown. In this work, we employed functional near-infrared spectroscopy (fNIRS) to introduce a methodological approach for quantifying the temporal delay of the evoked hemodynamic response. The method was validated during a vasodilatory task (breath-holding) in 50 CAS patients and 20 controls. Our results suggest that the hemodynamic response to breath-holding can be delayed by up to 6 s in the most severe patients, a significant increase from the median 4 s measured for the control group (p = 0.01). In addition, the fraction of brain regions that responded to the task decreased as the CAS severity increased, from a median of 90% in controls to 73% in the most severe CAS group (p = 0.04). The presence of collateral circulation increases the response to breath-holding and decreases the average time delays across the brain, although the number of communicating arteries alone cannot predict these fNIRS-based hemodynamic variables (p > 0.09). Overall, this work proposes a method to quantitatively assess impaired cerebral hemodynamics in CAS patients.

Optical imaging and spectroscopy for the study of the human brain: status report.

This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions.

Neurophotonic tools for microscopic measurements and manipulation: status report.

Neurophotonics was launched in 2014 coinciding with the launch of the BRAIN Initiative focused on development of technologies for advancement of neuroscience. For the last seven years, Neurophotonics' agenda has been well aligned with this focus on neurotechnologies featuring new optical methods and tools applicable to brain studies. While the BRAIN Initiative 2.0 is pivoting towards applications of these novel tools in the quest to understand the brain, this status report reviews an extensive and diverse toolkit of novel methods to explore brain function that have emerged from the BRAIN Initiative and related large-scale efforts for measurement and manipulation of brain structure and function. Here, we focus on neurophotonic tools mostly applicable to animal studies. A companion report, scheduled to appear later this year, will cover diffuse optical imaging methods applicable to noninvasive human studies. For each domain, we outline the current state-of-the-art of the respective technologies, identify the areas where innovation is needed, and provide an outlook for the future directions.

Effects of Systemic Physiology on Mapping Resting-State Networks Using Functional Near-Infrared Spectroscopy.

Resting-state functional connectivity (rsFC) has gained popularity mainly due to its simplicity and potential for providing insights into various brain disorders. In this vein, functional near-infrared spectroscopy (fNIRS) is an attractive choice due to its portability, flexibility, and low cost, allowing for bedside imaging of brain function. While promising, fNIRS suffers from non-neural signal contaminations (i.e., systemic physiological noise), which can increase correlation across fNIRS channels, leading to spurious rsFC networks. In the present work, we hypothesized that additional measurements with short channels, heart rate, mean arterial pressure, and end-tidal CO2 could provide a better understanding of the effects of systemic physiology on fNIRS-based resting-state networks. To test our hypothesis, we acquired 12 min of resting-state data from 10 healthy participants. Unlike previous studies, we investigated the efficacy of different pre-processing approaches in extracting resting-state networks. Our results are in agreement with previous studies and reinforce the fact that systemic physiology can overestimate rsFC. We expanded on previous work by showing that removal of systemic physiology decreases intra- and inter-subject variability, increasing the ability to detect neural changes in rsFC across groups and over longitudinal studies. Our results show that by removing systemic physiology, fNIRS can reproduce resting-state networks often reported with functional magnetic resonance imaging (fMRI). Finally, the present work details the effects of systemic physiology and outlines how to remove (or at least ameliorate) their contributions to fNIRS signals acquired at rest.

Differences in brain activity between fast and slow responses on psychomotor vigilance task: an fNIRS study.

Attention is a basic human function underlying every other cognitive process. It is demonstrated in the functional Magnetic Resonance Imaging literature that frontoparietal networks are involved with attentive performance while default mode networks are involved with inattentive performance. Yet, it is still not clear whether similar results would be found with functional Near-Infrared Spectroscopy. The goal of our study was to investigate differences in hemodynamic activity measured by functional Near-Infrared Spectroscopy between fast and slow responses on a simple sustained attention task both before and after stimulus onset. Thirty healthy adults took part in the study. Our results have shown differences between fast and slow responses only on channels over medial frontal cortex and inferior parietal cortex (p < 0,05). These differences were observed both before and after stimulus presentation. It is discussed that functional Near-Infrared Spectroscopy is a good tool to investigate the frontoparietal network and its relationship with performance in attention tasks; it could be used to further investigate other approaches on attention, such as the dual network model of cognitive control and brain states views based on complex systems analysis; and finally, it could be used to investigate attention in naturalistic settings.

Upcoming Neurophotonics Status Report.

Forthcoming status report articles provide updates on microscopy and on diffuse optical imaging in neurophotonics.

Blood flow response to orthostatic challenge identifies signatures of the failure of static cerebral autoregulation in patients with cerebrovascular disease.

BACKGROUND: The cortical microvascular cerebral blood flow response (CBF) to different changes in head-of-bed (HOB) position has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS) technique. However, the relationship between these relative ΔCBF changes and associated systemic blood pressure changes has not been studied, even though blood pressure is a major driver of cerebral blood flow. METHODS: Transcranial DCS data from four studies measuring bilateral frontal microvascular cerebral blood flow in healthy controls (n = 15), patients with asymptomatic severe internal carotid artery stenosis (ICA, n = 27), and patients with acute ischemic stroke (AIS, n = 72) were aggregated. DCS-measured CBF was measured in response to a short head-of-bed (HOB) position manipulation protocol (supine/elevated/supine, 5 min at each position). In a sub-group (AIS, n = 26; ICA, n = 14; control, n = 15), mean arterial pressure (MAP) was measured dynamically during the protocol. RESULTS: After elevated positioning, DCS CBF returned to baseline supine values in controls (p = 0.890) but not in patients with AIS (9.6% [6.0,13.3], mean 95% CI, p < 0.001) or ICA stenosis (8.6% [3.1,14.0], p = 0.003)). MAP in AIS patients did not return to baseline values (2.6 mmHg [0.5, 4.7], p = 0.018), but in ICA stenosis patients and controls did. Instead ipsilesional but not contralesional CBF was correlated with MAP (AIS 6.0%/mmHg [- 2.4,14.3], p = 0.038; ICA stenosis 11.0%/mmHg [2.4,19.5], p < 0.001). CONCLUSIONS: The observed associations between ipsilateral CBF and MAP suggest that short HOB position changes may elicit deficits in cerebral autoregulation in cerebrovascular disorders. Additional research is required to further characterize this phenomenon.

Accurate Image-guided (Re)Placement of NIRS Probes.

BACKGROUND AND OBJECTIVE: Functional near-infrared spectroscopy (fNIRS) has become an attractive choice to neuroscience because of its high temporal resolution, ease of use, non-invasiveness, and affordability. With the advent of wearable fNIRS technology, on-the-spot studies of brain function have become viable. However, the lack of within-subject reproducibility is one of the barriers to the full acceptability of fNIRS. To support the validation of the claim that within-subject reproducibility of fNIRS could benefit from accurate anatomical information, we present in this paper a method to develop an image-based system that improves the placement of the sensors on the scalp at interactive rates. METHODS: The proposed solution consists of an electromagnetic digitizer and an interactive visualization system that allows monitoring the movements of the digitizer on a real head with respect to the underlying cerebral cortical structures. GPU-based volume raycasting rendering is applied to unveil these structures from the corresponding magnetic resonance imaging volume. Scalp and cortical surface are estimated from the scanned volume to improve depth perception. An alignment algorithm between the real and scanned heads is devised to visually feedback the position of the stylus of the digitizer. Off-screen rendering of the depthmaps of the visible surfaces makes spatial positioning of a 2D interaction pointer possible. RESULTS: We evaluated the alignment accuracy using four to eight anatomical landmarks and found seven to be a good compromise between precision and efficiency. Next, we evaluated reproducibility in positioning five arbitrarily chosen points on three volunteers by four operators over five sessions. In every session, seven anatomical landmarks were applied in the alignment of the real and the scanned head. For the same volunteer, one-way analysis of variance (ANOVA) revealed no significant differences within the five points digitized by the same operator over five sessions (α = 0.05). In addition, preliminary study of motor cortex activation by right-hand finger tapping showed the potential of our approach to increase functional fNIRS reproducibility. CONCLUSIONS: Results of experiments suggest that the enhancement of the visualization of the location of the probes on the scalp, relative to the underlying cortical structures, improves reproducibility of fNIRS measurements. As further work, we plan to study the fNIRS reproducibility in other cortical regions and in clinical settings using the proposed system.

Real-Time Monitoring of Neurocritical Patients with Diffuse Optical Spectroscopies.

Neurophysiological monitoring is an important goal in the treatment of neurocritical patients, as it may prevent secondary damage and directly impact morbidity and mortality rates. However, there is currently a lack of suitable non-invasive, real-time technologies for continuous monitoring of cerebral physiology at the bedside. Diffuse optical techniques have been proposed as a potential tool for bedside measurements of cerebral blood flow and cerebral oxygenation in case of neurocritical patients. Diffuse optical spectroscopies have been previously explored to monitor patients in several clinical scenarios ranging from neonatal monitoring to cerebrovascular interventions in adults. However, the feasibility of the technique to aid clinicians by providing real-time information at the bedside remains largely unaddressed. Here, we report the translation of a diffuse optical system for continuous real-time monitoring of cerebral blood flow, cerebral oxygenation, and cerebral oxygen metabolism during intensive care. The real-time feature of the instrument could enable treatment strategies based on patient-specific cerebral physiology rather than relying on surrogate metrics, such as arterial blood pressure. By providing real-time information on the cerebral circulation at different time scales with relatively cheap and portable instrumentation, this approach may be especially useful in low-budget hospitals, in remote areas and for monitoring in open fields (e.g., defense and sports).

Integration of Spatial Information Increases Reproducibility in Functional Near-Infrared Spectroscopy.

As functional near-infrared spectroscopy (fNIRS) is developed as a neuroimaging technique and becomes an option to study a variety of populations and tasks, the reproducibility of the fNIRS signal is still subject of debate. By performing test-retest protocols over different functional tasks, several studies agree that the fNIRS signal is reproducible over group analysis, but the inter-subject and within-subject reproducibility is poor. The high variability at the first statistical level is often attributed to global systemic physiology. In the present work, we revisited the reproducibility of the fNIRS signal during a finger-tapping task across multiple sessions on the same and different days. We expanded on previous studies by hypothesizing that the lack of spatial information of the optodes contributes to the low reproducibility in fNIRS, and we incorporated a real-time neuronavigation protocol to provide accurate cortical localization of the optodes. Our proposed approach was validated in 10 healthy volunteers, and our results suggest that the addition of neuronavigation can increase the within-subject reproducibility of the fNIRS data, particularly in the region of interest. Unlike traditional approaches to positioning the optodes, in which low intra-subject reproducibility has been found, we were able to obtain consistent and robust activation of the contralateral primary motor cortex at the intra-subject level using a neuronavigation protocol. Overall, our findings support the hypothesis that at least part of the variability in fNIRS cannot be only attributed to global systemic physiology. The use of neuronavigation to guide probe positioning, as proposed in this work, has impacts to longitudinal protocols performed with fNIRS.

Real-Time Non-invasive Assessment of Cerebral Hemodynamics With Diffuse Optical Spectroscopies in a Neuro Intensive Care Unit: An Observational Case Study.

Prevention of secondary damage is an important goal in the treatment of severe neurological conditions, such as major head trauma or stroke. However, there is currently a lack of non-invasive methods for monitoring cerebral physiology. Diffuse optical methods have been proposed as an inexpensive, non-invasive bedside monitor capable of providing neurophysiology information in neurocritical patients. However, the reliability of the technique to provide accurate longitudinal measurement during the clinical evolution of a patient remains largely unaddressed. Here, we report on the translation of a hybrid diffuse optical system combining frequency domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS) for real-time monitoring of cerebral physiology in a neuro intensive care unit (neuro-ICU). More specifically, we present a case study of a patient admitted with a high-grade aneurysmal subarachnoid hemorrhage, who was monitored throughout hospitalization. We show that the neurophysiological parameters measured by diffuse optics at the bedside are consistent with the clinical evolution of the patient at all the different stages following its brain lesion. These data provide support for clinical translation of DOS/DCS as a useful biomarker of neurophysiology in the neuro-ICU, particularly in locations where other clinical resources are limited.

Functional near-infrared spectroscopy for speech protocols: characterization of motion artifacts and guidelines for improving data analysis.

Monitoring speech tasks with functional near-infrared spectroscopy (fNIRS) enables investigation of speech production mechanisms and informs treatment strategies for speech-related disorders such as stuttering. Unfortunately, due to movement of the temporalis muscle, speech production can induce relative movement between probe optodes and skin. These movements generate motion artifacts during speech tasks. In practice, spurious hemodynamic responses in functional activation signals arise from lack of information about the consequences of speech-related motion artifacts, as well as from lack of standardized processing procedures for fNIRS signals during speech tasks. To this end, we characterize the effects of speech production on fNIRS signals, and we introduce a systematic analysis to ameliorate motion artifacts. The study measured 50 healthy subjects performing jaw movement (JM) tasks and found that JM produces two different patterns of motion artifacts in fNIRS. To remove these unwanted contributions, we validate a hybrid motion-correction algorithm based sequentially on spline interpolation and then wavelet filtering. We compared performance of the hybrid algorithm with standard algorithms based on spline interpolation only and wavelet decomposition only. The hybrid algorithm corrected 94% of the artifacts produced by JM, and it did not lead to spurious responses in the data. We also validated the hybrid algorithm during a reading task performed under two different conditions: reading aloud and reading silently. For both conditions, we observed significant cortical activation in brain regions related to reading. Moreover, when comparing the two conditions, good agreement of spatial and temporal activation patterns was found only when data were analyzed using the hybrid approach. Overall, the study demonstrates a standardized processing scheme for fNIRS data during speech protocols. The scheme decreases spurious responses and intersubject variability due to motion artifacts.

Cerebral Blood Flow Response During Bolus Normal Saline Infusion After Ischemic Stroke.

GOALS: We quantified cerebral blood flow response to a 500 cc bolus of 0.9%% normal saline (NS) within 96 hours of acute ischemic stroke (AIS) using diffuse correlation spectroscopy (DCS). MATERIALS AND METHODS: Subjects with AIS in the anterior, middle, or posterior cerebral artery territory were enrolled within 96 hours of symptom onset. DCS measured relative cerebral blood flow (rCBF) in the bilateral frontal lobes for 15 minutes at rest (baseline), during a 30-minute infusion of 500 cc NS (bolus), and for 15 minutes after completion (post-bolus). Mean rCBF for each time period was calculated for individual subjects and median rCBF for the population was compared between time periods. Linear regression was used to evaluate for associations between rCBF and clinical features. RESULTS: Among 57 subjects, median rCBF (IQR) increased relative to baseline in the ipsilesional hemisphere by 17% (-2.0%, 43.1%), P< 0.001, and in the contralesional hemisphere by 13.3% (-4.3%, 36.0%), P < .004. No significant associations were found between ipsilesional changes in rCBF and age, race, infarct size, infarct location, presence of large vessel stenosis, NIH stroke scale, or symptom duration. CONCLUSION: A 500 cc bolus of .9% NS produced a measurable increase in rCBF in both the affected and nonaffected hemispheres. Clinical features did not predict rCBF response.

Perfusion Enhancement with Respiratory Impedance After Stroke (PERI-Stroke).

Intrathoracic pressure influences cardiac output and may affect cerebral blood flow (CBF). We aimed to quantify the cerebral hemodynamic response to intrathoracic pressure reduction in patients with acute ischemic stroke using a noninvasive respiratory impedance (RI) device. We assessed low-level (6 cm H2O) and high-level (12 cm H2O) RI in 17 spontaneously breathing patients within 72 h of anterior circulation acute ischemic stroke. Average age was 65 years, and 35% were female. Frontal lobe tissue perfusion and middle cerebral artery velocity (MCAv) were continuously monitored with optical diffuse correlation spectroscopy (DCS) and transcranial Doppler ultrasound, respectively. High-level RI resulted in a 7% increase in MCAv (p = 0.004). MCAv varied across all studied levels (baseline vs low-level vs high-level, p = 0.006), with a significant test of trend (p = 0.002). Changes were not seen in DCS measured tissue perfusion by nonparametric pairwise comparison. Mixed effects regression analysis identified a small increase in both MCAv (low-level RI: ß 2.1, p < 0.001; high-level RI: ß 5.0, p < 0.001) and tissue-level flow (low-level RI: ß 5.4, p < 0.001; high-level RI: ß 5.9, p < 0.001). There was a small increase in mean arterial pressure during low-level and high-level RI, 4% (p = 0.013) and 4% (p = 0.017), respectively. End-tidal CO2 remained stable throughout the protocol. RI was well tolerated. Manipulating intrathoracic pressure via noninvasive RI was safe and produced a small but measurable increase in cerebral perfusion in acute ischemic stroke patients. Future studies are warranted to assess whether RI is feasible and tolerable for prolonged use in hyperacute stroke management.

Changes of functional response in sensorimotor cortex of preterm and full-term infants during the first year: An fNIRS study.

BACKGROUND: Motor impairments are frequently associated with preterm birth and interfere in acquisition of essential skills to global development. Using Near Infrared Spectroscopy (NIRS), the study of neural correlates of motor development in early stages of life are feasible in an ecological assessment. AIMS: To evaluate changes in cortical activity in response to a sensorimotor stimulation in preterm and full-term infants at 6 and 12 months of age. STUDY DESIGN: A longitudinal study was conducted with 22 infants (12 preterm and 10 full-term). Hemodynamic activity during sensorimotor task (8 blocks of 8 s of vibration applied to infant's right hand) was measured by Functional Near Infrared Spectroscopy (fNIRS). The optical probe consisted of 84 channels positioned according to the international 10-20 system coordinates, covering the frontal (38 channels), parietal (16 channels), temporal (22 channels) and occipital (8 channels) lobes of both hemispheres. RESULTS: Preterm and full-term infants exhibited differences of location of the activation as well on the hemodynamic response in both the evaluated age groups. CONCLUSIONS: Group differences in activation of sensorimotor cortex observed in this study demonstrate the potential of fNIRS application for preterm evaluation of motor development in children. Overall, the present work contributes to our understanding of cortical activation of cerebral motor skills spanning early ages in preterm-born children.