In vivo measure of neonate brain optical properties and hemodynamic parameters by time-domain near-infrared spectroscopy.

By exploiting a multichannel portable instrument for time-domain near-infrared spectroscopy (TD-NIRS), we characterized healthy neonates' brains in term of optical properties and hemodynamic parameters. In particular, we assessed the absolute values of the absorption and reduced scattering coefficients at two wavelengths, together with oxy-, deoxy- and total hemoglobin concentrations, and the blood oxygen saturation of the neonates' brains. In this study, 33 healthy full-term neonates were tested, obtaining the following median values: 0.28 and [Formula: see text] for [Formula: see text] at 690 and 820 nm, respectively; 5.8 and [Formula: see text] for [Formula: see text] at 690 and 820 nm, respectively; [Formula: see text] for [Formula: see text]; [Formula: see text] for [Formula: see text]; [Formula: see text] for [Formula: see text]; 72% for [Formula: see text]. In general, the agreement of these values with the sparse existing literature appears not always consistent. These findings demonstrate the first measurements of optical properties of the healthy neonate brain using TD-NIRS and show the need for clarification of optical properties across methods and populations.

Effect of a thin superficial layer on the estimate of hemodynamic changes in a two-layer medium by time domain NIRS.

In order to study hemodynamic changes involved in muscular metabolism by means of time domain fNIRS, we need to discriminate in the measured signal contributions coming from different depths. Muscles are, in fact, typically located under other tissues, e.g. skin and fat. In this paper, we study the possibility to exploit a previously proposed method for analyzing time-resolved fNIRS measurements in a two-layer structure with a thin superficial layer. This method is based on the calculation of the time-dependent mean partial pathlengths. We validated it by simulating venous and arterial arm cuff occlusions and then applied it on in vivo measurements.

Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study.

Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

Linear regression models and k-means clustering for statistical analysis of fNIRS data.

We propose a new algorithm, based on a linear regression model, to statistically estimate the hemodynamic activations in fNIRS data sets. The main concern guiding the algorithm development was the minimization of assumptions and approximations made on the data set for the application of statistical tests. Further, we propose a K-means method to cluster fNIRS data (i.e. channels) as activated or not activated. The methods were validated both on simulated and in vivo fNIRS data. A time domain (TD) fNIRS technique was preferred because of its high performances in discriminating cortical activation and superficial physiological changes. However, the proposed method is also applicable to continuous wave or frequency domain fNIRS data sets.

Performance assessment of time-domain optical brain imagers, part 1: basic instrumental performance protocol.

Performance assessment of instruments devised for clinical applications is of key importance for validation and quality assurance. Two new protocols were developed and applied to facilitate the design and optimization of instruments for time-domain optical brain imaging within the European project nEUROPt. Here, we present the "Basic Instrumental Performance" protocol for direct measurement of relevant characteristics. Two tests are discussed in detail. First, the responsivity of the detection system is a measure of the overall efficiency to detect light emerging from tissue. For the related test, dedicated solid slab phantoms were developed and quantitatively spectrally characterized to provide sources of known radiance with nearly Lambertian angular characteristics. The responsivity of four time-domain optical brain imagers was found to be of the order of 0.1 m² sr. The relevance of the responsivity measure is demonstrated by simulations of diffuse reflectance as a function of source-detector separation and optical properties. Second, the temporal instrument response function (IRF) is a critically important factor in determining the performance of time-domain systems. Measurements of the IRF for various instruments were combined with simulations to illustrate the impact of the width and shape of the IRF on contrast for a deep absorption change mimicking brain activation.

Performance assessment of time-domain optical brain imagers, part 2: nEUROPt protocol.

The nEUROPt protocol is one of two new protocols developed within the European project nEUROPt to characterize the performances of time-domain systems for optical imaging of the brain. It was applied in joint measurement campaigns to compare the various instruments and to assess the impact of technical improvements. This protocol addresses the characteristic of optical brain imaging to detect, localize, and quantify absorption changes in the brain. It was implemented with two types of inhomogeneous liquid phantoms based on Intralipid and India ink with well-defined optical properties. First, small black inclusions were used to mimic localized changes of the absorption coefficient. The position of the inclusions was varied in depth and lateral direction to investigate contrast and spatial resolution. Second, two-layered liquid phantoms with variable absorption coefficients were employed to study the quantification of layer-wide changes and, in particular, to determine depth selectivity, i.e., the ratio of sensitivities for deep and superficial absorption changes. We introduce the tests of the nEUROPt protocol and present examples of results obtained with different instruments and methods of data analysis. This protocol could be a useful step toward performance tests for future standards in diffuse optical imaging.

Time domain functional NIRS imaging for human brain mapping.

This review is aimed at presenting the state-of-the-art of time domain (TD) functional near-infrared spectroscopy (fNIRS). We first introduce the physical principles, the basics of modeling and data analysis. Basic instrumentation components (light sources, detection techniques, and delivery and collection systems) of a TD fNIRS system are described. A survey of past, existing and next generation TD fNIRS systems used for research and clinical studies is presented. Performance assessment of TD fNIRS systems and standardization issues are also discussed. Main strengths and weakness of TD fNIRS are highlighted, also in comparison with continuous wave (CW) fNIRS. Issues like quantification of the hemodynamic response, penetration depth, depth selectivity, spatial resolution and contrast-to-noise ratio are critically examined, with the help of experimental results performed on phantoms or in vivo. Finally we give an account on the technological developments that would pave the way for a broader use of TD fNIRS in the neuroimaging community.

Neurophotonics: non-invasive optical techniques for monitoring brain functions.

The aim of this review is to present the state of the art of neurophotonics, a recently founded discipline lying at the interface between optics and neuroscience. While neurophotonics also includes invasive techniques for animal studies, in this review we focus only on the non-invasive methods that use near infrared light to probe functional activity in the brain, namely the fast optical signal, diffuse correlation spectroscopy, and functional near infrared spectroscopy methods. We also present an overview of the physical principles of light propagation in biological tissues, and of the main physiological sources of signal. Finally, we discuss the open issues in models, instrumentation, data analysis and clinical approaches.

Multi-channel medical device for time domain functional near infrared spectroscopy based on wavelength space multiplexing.

We have designed a compact dual wavelength (687 nm, 826 nm) multi-channel (16 sources, 8 detectors) medical device for muscle and brain imaging based on time domain functional near infrared spectroscopy. The system employs the wavelength space multiplexing approach to reduce wavelength cross-talk and increase signal-to-noise ratio. System performances have been tested on homogeneous and heterogeneous tissue phantoms following specifically designed protocols for photon migration instruments. Preliminary in vivo measurements have been performed to validate the instrument capability to monitor hemodynamic parameters changes in the arm muscle during arterial occlusion and in the adult head during a motor task experiment.

Cerebral cortex activation mapping upon electrical muscle stimulation by 32-channel time-domain functional near-infrared spectroscopy.

The application of different EMS current thresholds on muscle activates not only the muscle but also peripheral sensory axons that send proprioceptive and pain signals to the cerebral cortex. A 32-channel time-domain fNIRS instrument was employed to map regional cortical activities under varied EMS current intensities applied on the right wrist extensor muscle. Eight healthy volunteers underwent four EMS at different current thresholds based on their individual maximal tolerated intensity (MTI), i.e., 10 % < 50 % < 100 % < over 100 % MTI. Time courses of the absolute oxygenated and deoxygenated hemoglobin concentrations primarily over the bilateral sensorimotor cortical (SMC) regions were extrapolated, and cortical activation maps were determined by general linear model using the NIRS-SPM software. The stimulation-induced wrist extension paradigm significantly increased activation of the contralateral SMC region according to the EMS intensities, while the ipsilateral SMC region showed no significant changes. This could be due in part to a nociceptive response to the higher EMS current intensities and result also from increased sensorimotor integration in these cortical regions.

Method for the discrimination of superficial and deep absorption variations by time domain fNIRS.

A method for the discrimination of superficial and deep absorption variations by time domain functional near infrared spectroscopy is presented. The method exploits the estimate of the photon time-dependent pathlength in different domains of the sampled medium and makes use of an approach based on time-gating of the photon distribution of time-of-flights. Validation of the method is performed in the two-layer geometry to focus on muscle and head applications. Numerical simulations varied the thickness of the upper layer, the interfiber distance, the shape of the instrument response function and the photon counts. Preliminary results from in vivo data are also shown.