Depth Sensitivity and Source-Detector Separations for Near Infrared Spectroscopy Based on the Colin27 Brain Template

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

Complete head cerebral sensitivity mapping for diffuse correlation spectroscopy using subject-specific magnetic resonance imaging models

We characterize cerebral sensitivity across the entire adult human head for diffuse correlation spectroscopy, an optical technique increasingly used for bedside cerebral perfusion monitoring. Sixteen subject-specific magnetic resonance imaging-derived head models were used to identify high sensitivity regions by running Monte Carlo light propagation simulations at over eight hundred uniformly distributed locations on the head. Significant spatial variations in cerebral sensitivity, consistent across subjects, were found. We also identified correlates of such differences suitable for real-time assessment. These variations can be largely attributed to changes in extracerebral thickness and should be taken into account to optimize probe placement in experimental settings

Impact of Anatomical Variability on Sensitivity Profile in fNIRS-MRI Integration

Functional near-infrared spectroscopy (fNIRS) is an important non-invasive technique used to monitor cortical activity. However, a varying sensitivity of surface channels vs. cortical structures may suggest integrating the fNIRS with the subject-specific anatomy (SSA) obtained from routine MRI. Actual processing tools permit the computation of the SSA forward problem (i.e., cortex to channel sensitivity) and next, a regularized solution of the inverse problem to map the fNIRS signals onto the cortex. The focus of this study is on the analysis of the forward problem to quantify the effect of inter-subject variability. Thirteen young adults (six males, seven females, age 29.3 +/- 4.3) underwent both an MRI scan and a motor grasping task with a continuous wave fNIRS system of 102 measurement channels with optodes placed according to a 10/5 system. The fNIRS sensitivity profile was estimated using Monte Carlo simulations on each SSA and on three major atlases (i.e., Colin27, ICBM152 and FSAverage) for comparison. In each SSA, the average sensitivity curves were obtained by aligning the 102 channels and segmenting them by depth quartiles. The first quartile (depth < 11.8 (0.7) mm, median (IQR)) covered 0.391 (0.087)% of the total sensitivity profile, while the second one (depth < 13.6 (0.7) mm) covered 0.292 (0.009)%, hence indicating that about 70% of the signal was from the gyri. The sensitivity bell-shape was broad in the source-detector direction (20.953 (5.379) mm FWHM, first depth quartile) and steeper in the transversal one (6.082 (2.086) mm). The sensitivity of channels vs. different cortical areas based on SSA were analyzed finding high dispersions among subjects and large differences with atlas-based evaluations. Moreover, the inverse cortical mapping for the grasping task showed differences between SSA and atlas based solutions. In conclusion, integration with MRI SSA can significantly improve fNIRS interpretation

Noninvasive optical estimation of CSF thickness for brain-atrophy monitoring

Dementia disorders are increasingly becoming sources of a broad range of problems, strongly interfering with normal daily tasks of a growing number of individuals. Such neurodegenerative diseases are often accompanied with progressive brain atrophy that, at late stages, leads to drastically reduced brain dimensions. At the moment, this structural involution can be followed with XCT or MRI measurements that share numerous disadvantages in terms of usability, invasiveness and costs. In this work, we aim to retrieve information concerning the brain atrophy stage and its evolution, proposing a novel approach based on non-invasive time-resolved Near Infra-Red (tr-NIR) measurements. For this purpose, we created a set of human-head atlases, in which we eroded the brain as it would happen in a clinical brain-atrophy progression. With these realistic meshes, we reproduced a longitudinal tr-NIR study exploiting a Monte-Carlo photon propagation algorithm to model the varying cerebral spinal fluid (CSF). The study of the time-resolved reflectance curve at late photon arrival times exhibited peculiar slope-changes upon CSF layer increase that were confirmed under several measurement conditions. The performance of the technique suggests good sensitivity to CSF variation, useful for a fast and non-invasive observation of the dementia progression.Comment: 32 pages, double spaced, 11 figure

The Temporal Confounding Effects of Extra-cerebral Contamination Factors on the Hemodynamic Signal Measured by Functional Near-Infrared Spectroscopy

Introduction: Functional near-infrared spectroscopy (fNIRS) has been broadly applied for optical brain imaging. This method is hemodynamic-based functional brain imaging relying on the measurement of the neurovascular coupling to detect changes in cerebral neuronal activities. The extra-cerebral hemodynamic changes are important contaminating factors in fNIRS measurements. This error signal can be misinterpreted as cerebral activities during fNIRS studies. Recently, it was assumed that temporal changes in deoxygenated hemoglobin concentration [HHb] was hardly affected by superficial blood flow, and it was proposed that the activation maps could be determined from [HHb] at large source-detector separation.Methods: In the current study, we measured the temporal changes in [HHb] using a continues-wave fNIRS device at large source-detector separation, while superficial blood flow was stimulated by infrared lasers. A mesh-based Monte Carlo code was applied to estimate fNIRS sensitivity to superficial hemodynamic changes in a realistic 3D MRI-based brain phantom.Results: First, we simulated photon migration in a four-layered human-head slab model to calculate PPLs and fNIRS sensitivity. Then, the localization of the infrared laser inside a realistic brain model was studied using the Monte Carlo method. Finally, the changes in [HHb] over the prefrontal cortex of six adult males were measured by fNIRS at a source-detector separation of 3 cm. The results demonstrated that the relation between fNIRS sensitivity and an increase in S-D separation was nonlinear and a correlation between shallow and deep signals was observed.Conclusion: The presented results demonstrated that the temporal changes in the superficial blood flow could strongly affect HHb measurement at large source-detector separation. Hence, the cerebral activity map extracted from the [HHb] signal was mainly contaminated by superficial blood flow

T1 Magnetic Resonance Imaging Head Segmentation for Diffuse Optical Tomography and Electroencephalography

Accurate segmentation of structural magnetic resonance images is critical for creating subject-specific forward models for functional neuroimaging source localization. In this work, we present an innovative segmentation algorithm that generates accurate head tissue layer thicknesses that are needed for diffuse optical tomography (DOT) data analysis. The presented algorithm is compared against other publicly available head segmentation methods. The proposed algorithm has a root mean square scalp thickness error of 1.60 mm, skull thickness error of 1.96 mm, and summed scalp and skull error of 1.49 mm. We also introduce a segmentation evaluation metric that evaluates the accuracy of tissue layer thicknesses in regions of the head where optodes are typically placed. The presented segmentation algorithm and evaluation metric are tools for improving the localization accuracy of neuroimaging with DOT, and also multimodal neuroimaging such as combined electroencephalography and DOT

Surface-based integration approach for fNIRS-fMRI reliability assessment

Introduction: Studies integrating functional near-infrared spectroscopy (fNIRS) with functional MRI (fMRI) employ heterogeneous methods in defining common regions of interest in which similarities are assessed. Therefore, spatial agreement and temporal correlation may not be reproducible across studies. In the present work, we address this issue by proposing a novel method for integration and analysis of fNIRS and fMRI over the cortical surface. Materials and methods: Eighteen healthy volunteers (age mean±SD 30.55 ± 4.7, 7 males) performed a motor task during non-simultaneous fMRI and fNIRS acquisitions. First, fNIRS and fMRI data were integrated by projecting subject- and group-level source maps over the cortical surface mesh to define anatomically constrained functional ROIs (acfROI). Next, spatial agreement and temporal correlation were quantified as Dice Coefficient (DC) and Pearson's correlation coefficient between fNIRS-fMRI in the acfROIs. Results: Subject-level results revealed moderate to substantial spatial agreement (DC range 0.43 - 0.64), confirmed at the group-level only for blood oxygenation level-dependent (BOLD) signal vs. HbO2 (0.44 - 0.69), while lack of agreement was found for BOLD vs. HbR in some instances (0.05 - 0.49). Subject-level temporal correlation was moderate to strong (0.79 - 0.85 for BOLD vs. HbO2 and -0.62 to -0.72 for BOLD vs. HbR), while an overall strong correlation was found for group-level results (0.95 - 0.98 for BOLD vs. HbO2 and -0.91 to -0.94 for BOLD vs. HbR). Conclusion: The proposed method directly compares fNIRS and fMRI by projecting individual source maps to the cortical surface. Our results indicate spatial and temporal correspondence between fNIRS and fMRI, and promotes the use of fNIRS when more ecological acquision settings are required, such as longitudinal monitoring of brain activity before and after rehabilitation

Shining a Light on Awareness::A Review of Functional Near-Infrared Spectroscopy for Prolonged Disorders of Consciousness

Qualitative clinical assessments of the recovery of awareness after severe brain injury require an assessor to differentiate purposeful behavior from spontaneous behavior. As many such behaviors are minimal and inconsistent, behavioral assessments are susceptible to diagnostic errors. Advanced neuroimaging tools can bypass behavioral responsiveness and reveal evidence of covert awareness and cognition within the brains of some patients, thus providing a means for more accurate diagnoses, more accurate prognoses, and, in some instances, facilitated communication. The majority of reports to date have employed the neuroimaging methods of functional magnetic resonance imaging, positron emission tomography, and electroencephalography (EEG). However, each neuroimaging method has its own advantages and disadvantages (e.g., signal resolution, accessibility, etc.). Here, we describe a burgeoning technique of non-invasive optical neuroimaging—functional near-infrared spectroscopy (fNIRS)—and review its potential to address the clinical challenges of prolonged disorders of consciousness. We also outline the potential for simultaneous EEG to complement the fNIRS signal and suggest the future directions of research that are required in order to realize its clinical potential

False positives and false negatives in functional near-infrared spectroscopy: issues, challenges, and the way forward

We highlight a significant problem that needs to be considered and addressed when performing functional near-infrared spectroscopy (fNIRS) studies, namely the possibility of inadvertently measuring fNIRS hemodynamic responses that are not due to neurovascular coupling. These can be misinterpreted as brain activity, i.e., "false positives" (errors caused by wrongly assigning a detected hemodynamic response to functional brain activity), or mask brain activity, i.e., "false negatives" (errors caused by wrongly assigning a not observed hemodynamic response in the presence of functional brain activity). Here, we summarize the possible physiological origins of these issues and suggest ways to avoid and remove them