Hyperspectral near-infrared spectroscopy assessment of the brain during hypoperfusion.

Two-thirds of out-of-hospital cardiac arrest patients, who survive to hospital admission, die in the hospital from neurological injuries related to cerebral hypoperfusion. Therefore, noninvasive real-time monitoring of the cerebral oxygen metabolism in cardiac arrest patients is extremely important. Hyperspectral near-infrared spectroscopy (hNIRS) is a noninvasive technique that measures concentrations of the key chromophores in the brain, such as oxygenated hemoglobin, deoxygenated hemoglobin, and cytochrome C oxidase (CCO), an intracellular marker of oxygen consumption. We tested hNIRS on 10 patients undergoing transcatheter aortic valve insertion, where rapid ventricular pacing (RVP) is required to temporarily induce sudden hypotension and hypoperfusion that mimic cardiac arrest. Using multidistance hNIRS, we found that tissue oxygen saturation changes in the cerebral tissue were lower than those in the scalp during RVP. CCO redox changes were detected in cerebral tissue but not in the scalp during RVP. We have demonstrated that hNIRS is feasible and can detect sudden changes in cerebral oxygenation and metabolism in patients during profound hypotension.

Study of the Effects of Epinephrine on Cerebral Oxygenation and Metabolism During Cardiac Arrest and Resuscitation by Hyperspectral Near-Infrared Spectroscopy.

OBJECTIVES: Epinephrine is routinely administered to sudden cardiac arrest patients during resuscitation, but the neurologic effects on patients treated with epinephrine are not well understood. This study aims to assess the cerebral oxygenation and metabolism during ventricular fibrillation cardiac arrest, cardiopulmonary resuscitation, and epinephrine administration. DESIGN: To investigate the effects of equal dosages of IV epinephrine administrated following sudden cardiac arrest as a continuous infusion or successive boluses during cardiopulmonary resuscitation, we monitored cerebral oxygenation and metabolism using hyperspectral near-infrared spectroscopy. SETTINGS: A randomized laboratory animal study. SUBJECTS: Nine healthy pigs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our study showed that although continuous epinephrine administration had no significant impact on overall cerebral hemodynamics, epinephrine boluses transiently improved cerebral oxygenation (oxygenated hemoglobin) and metabolism (cytochrome c oxidase) by 15% ± 6.7% and 49% ± 18%, respectively (p < 0.05) compared with the baseline (untreated) ventricular fibrillation. Our results suggest that the effects of epinephrine diminish with successive boluses as the impact of the third bolus on brain oxygen metabolism was 24.6% ± 3.8% less than that of the first two boluses. CONCLUSIONS: Epinephrine administration by bolus resulted in transient improvements in cerebral oxygenation and metabolism, whereas continuous epinephrine infusion did not, compared with placebo. Future studies are needed to evaluate and optimize the use of epinephrine in cardiac arrest resuscitation, particularly the dose, timing, and mode of administration.

Wavelength optimization in the multispectral photoacoustic tomography of the lymphatic drainage in mice.

Multispectral photoacoustic tomography provides mapping of the tissue chromophore distributions using sets of tunable laser wavelengths. With the overall goal of studying the dynamics of cerebrospinal fluid in mice in vivo, our work aims to minimize the number of wavelengths to reduce scanning time, improve the temporal resolution, reduce the energy deposition and avoid the tracer photobleaching while maintaining high image quality. To select small sets of wavelengths we directly searched for the combinations of wavelengths providing the best and worst image quality in comparison with a reference image obtained using 131 closely spaced wavelengths between 680 and 940 nm in terms of the peak signal-to-noise ratio (PSNR). We have shown that using the PSNR optimization method, additional improvements could be achieved over the wavelength set selected using the method of the minimization of the extinction matrix condition number.

Cerebral Hemodynamics and Metabolism During Cardiac Arrest and Cardiopulmonary Resuscitation Using Hyperspectral Near Infrared Spectroscopy.

BACKGROUND: Maintaining cerebral oxygen delivery and metabolism during cardiac arrest (CA) through resuscitation is essential to improve the survival rate while avoiding brain injury. The effect of CA and cardiopulmonary resuscitation (CPR) on cerebral and muscle oxygen delivery and metabolism is not clearly quantified.Methods and Results:A novel hyperspectral near-infrared spectroscopy (hNIRS) technique was developed and evaluated to measure cerebral oxygen delivery and aerobic metabolism during ventricular fibrillation (VF) CA and CPR in 14 pigs. The hNIRS parameters were measured simultaneously on the dura and skull to investigate the validity of non-invasive hNIRS measurements. In addition, we compared the hNIRS data collected simultaneously on the brain and muscle. Following VF induction, oxygenated hemoglobin (HbO2) declined with a 9.9 s delay and then cytochrome-c-oxidase (Cyt-ox) decreased on average 4.4 s later (P<0.05). CPR improved cerebral metabolism, which was reflected by an average 0.4 µmol/L increase in Cyt-ox, but had no significant effect on HbO2, deoxygenated hemoglobin (HHb) and tissue oxygen saturation (tSO2). Cyt-ox had greater correlation with HHb than HbO2. Muscle metabolism during VF and CPR was significantly different from that of the brain. The total hemoglobin concentration (in the brain only) increased after ~200 s of untreated CA, which is most likely driven by cerebral autoregulation through vasodilation. CONCLUSIONS: Overall, hNIRS showed consistent measurements of hemodynamics and metabolism during CA and CPR.

Event-related changes of the prefrontal cortex oxygen delivery and metabolism during driving measured by hyperspectral fNIRS.

Recent technological advancements in optical spectroscopy allow for the construction of hyperspectral (broadband) portable tissue oximeters. In a series of our recent papers we have shown that hyperspectral NIRS (hNIRS) has similar or better capabilities in the absolute tissue oximetry as frequency-domain NIRS, and that hNIRS is also very efficient in measuring temporal changes in tissue hemoglobin concentration and oxygenation. In this paper, we extend the application of hNIRS to the measurement of event-related hemodynamic and metabolic functional cerebral responses during simulated driving. In order to check if hNIRS can detect event-related changes in the brain, we measured the concentration changes of oxygenated (HbO2) and deoxygenated (HHb) hemoglobin and of the oxidized state of cytochrome c oxidase, on the right and left prefrontal cortices (PFC) simultaneously during simulated driving on sixteen healthy right-handed participants (aged between 22-32). We used our in-house hNIRS system based on a portable spectrometer with cooled CCD detector and a driving simulator with a fully functional steering wheel and foot pedals. Each participant performed different driving tasks and participants were distracted during some driving conditions by asking general knowledge true/false questions. Our findings suggest that more complex driving tasks (non-distracted) deactivate PFC while distractions during driving significantly activate PFC, which is in agreement with previous fMRI results. Also, we found the changes in the redox state of the cytochrome C oxidase to be very consistent with those in the concentrations of HbO2 and HHb. Overall our findings suggest that in addition to the suitability of absolute tissue oximetry, hyperspectral NIRS may also offer advantages in functional brain imaging. In particular, it can be used to measure the metabolic functional brain activity during actual driving.

Development of a combined broadband near-infrared and diffusion correlation system for monitoring cerebral blood flow and oxidative metabolism in preterm infants.

Neonatal neuromonitoring is a major clinical focus of near-infrared spectroscopy (NIRS) and there is an increasing interest in measuring cerebral blood flow (CBF) and oxidative metabolism (CMRO2) in addition to the classic tissue oxygenation saturation (StO2). The purpose of this study was to assess the ability of broadband NIRS combined with diffusion correlation spectroscopy (DCS) to measured changes in StO2, CBF and CMRO2 in preterm infants undergoing pharmaceutical treatment of patent ductus arteriosus. CBF was measured by both DCS and contrast-enhanced NIRS for comparison. No significant difference in the treatment-induced CBF decrease was found between DCS (27.9 ± 2.2%) and NIRS (26.5 ± 4.3%). A reduction in StO2 (70.5 ± 2.4% to 63.7 ± 2.9%) was measured by broadband NIRS, reflecting the increase in oxygen extraction required to maintain CMRO2. This study demonstrates the applicability of broadband NIRS combined with DCS for neuromonitoring in this patient population.

Improved light collection and wavelet de-noising enable quantification of cerebral blood flow and oxygen metabolism by a low-cost, off-the-shelf spectrometer.

Broadband continuous-wave near-infrared spectroscopy (CW-NIRS) is an attractive alternative to time-resolved and frequency-domain techniques for quantifying cerebral blood flow (CBF) and oxygen metabolism in newborns. However, efficient light collection is critical to broadband CW-NIRS since only a small fraction of the injected light emerges from any given area of the scalp. Light collection is typically improved by optimizing the contact area between the detection system and the skin by means of light guides with large detection surface. Since the form-factor of these light guides do not match the entrance of commercial spectrometers, which are usually equipped with a narrow slit to improve their spectral resolution, broadband NIRS spectrometers are typically custom-built. Nonetheless, off-the-shelf spectrometers have attractive advantages compared to custom-made units, such as low cost, small footprint, and wide availability. We demonstrate that off-the-shelf spectrometers can be easily converted into suitable instruments for deep tissue spectroscopy by improving light collection, while maintaining good spectral resolution, and reducing measurement noise. The ability of this approach to provide reliable cerebral hemodynamics was illustrated in a piglet by measuring CBF and oxygen metabolism under different anesthetic regimens.

Broadband continuous-wave technique to measure baseline values and changes in the tissue chromophore concentrations.

We present a broad-band, continuous-wave spectral approach to quantify the baseline optical properties of tissue and changes in the concentration of a chromophore, which can assist to quantify the regional blood flow from dynamic contrast-enhanced near-infrared spectroscopy data. Experiments were conducted on phantoms and piglets. The baseline optical properties of tissue were determined by a multi-parameter wavelength-dependent data fit of a photon diffusion equation solution for a homogeneous medium. These baseline optical properties were used to find the changes in Indocyanine green concentration time course in the tissue. The changes were obtained by fitting the dynamic data at the peak wavelength of the chromophore absorption, which were used later to estimate the cerebral blood flow using a bolus tracking method.

Independent component analysis of broadband near-infrared spectroscopy data acquired on adult human head.

The goal of this study was to investigate the ability of independent component analysis in the time-spectral domain to isolate physiological sources of functional near infrared spectroscopy signals. We apply independent component analysis to the broadband fNIRS data acquired on the human forehead at 650 different wavelengths between 700 nm and 950 nm. To induce cerebral oxygenation changes we use the breath holding paradigm. We found one major independent component during baseline and two major components during exercise. Each independent component corresponds to one oxy-hemoglobin and one deoxy-hemoglobin time courses. The corresponding characteristic spectra of changes in optical absorption suggested that one component represented vasodilation of cerebral arterioles while the delayed component represented the washout of deoxyhemoglobin either in cerebral capillaries and venules or in extra cerebral tissue. We found that both broadband and isolated wavelength data can produce similar independent components.

Correlation of functional and resting state connectivity of cerebral oxy-, deoxy-, and total hemoglobin concentration changes measured by near-infrared spectrophotometry.

The aim is to study cerebral vascular functional connectivity during motor tasks and resting state using multichannel frequency-domain near-infrared spectrophotometry. Maps of 5.7 × 10.8 cm size displaying changes in cerebral oxyhemoglobin (O(2)Hb), deoxyhemoglobin (HHb), and total hemoglobin (tHb) concentrations were measured in the motor cortex in 12 subjects (mean age of 28.8±12.7 yrs) during resting state and during two palm squeezing tasks with different timing. For each condition, phase plane plots, cross correlation functions, and connectivity indices were generated for O(2)Hb, HHb, and tHb. The amplitude of the concentration changes in O(2)Hb and HHb depends on the age of the subject. We found large regions of connectivity, which were similar for resting state and task conditions. This means the spatial relationships during resting state, when changes in O(2)Hb, HHb, and tHb corresponded to spontaneous oscillations, were correlated to the spatial patterns during the activation tasks, when changes in O(2)Hb, HHb, and tHb concentration were related to the alternation of stimulation and rest. Thus, the vascular functional connectivity was also present during resting state. The findings suggest that the vascular response to functional activation may be a nonlinear synchronization phenomenon and that resting state processes are more important than previously expected.

Measurement of the optical properties of a two-layer model of the human head using broadband near-infrared spectroscopy.

We present the development of a continuous-wave method of quantifying the optical properties of a two-layered model of the human head using a broadband spectral approach. Absolute absorption and scattering properties of the upper and lower layers of phantoms with known optical properties were reconstructed from steady-state multi-distance measurements by performing differential fit analysis of the near-infrared reflectance spectrum between 700 and 1000 nm. From spectra acquired at 10, 20, and 30 mm, the concentration of a chromophore in the bottom layer was determined within an error of 10% in the presence of a 15 mm thick top layer. These results demonstrate that our method was able to determine the optical properties of the lower layer, which represents brain, with acceptable error at specific source-detector distances.

Optimal quantitation of the cerebral hemodynamic response in functional near-infrared spectroscopy.

We have compared cerebral hemodynamic changes measured by near-infrared spectroscopy (NIRS) with simultaneously acquired BOLD fMRI signals during breath hold challenge in humans. The oxy- and deoxyhemoglobin concentration changes were obtained from the same broadband NIRS data using four different quantitation methods. One method used only two wavelengths (690 nm and 830 nm), and three other methods used broadband data with different spectral fitting algorithms. We found that the broadband techniques employing spectral derivatives were significantly superior to the multi-wavelength methods in terms of the correlation with the BOLD signals. In two cases out of six we found that the time courses of the deoxyhemoglobin changes produced by the two-wavelength method were qualitatively inconsistent with the BOLD fMRI signals.

A spatial and temporal comparison of hemodynamic signals measured using optical and functional magnetic resonance imaging during activation in the human primary visual cortex.

Functional near infrared spectro-imaging (fNIRSI) is potentially a very useful technique for obtaining information about the underlying physiology of the blood oxygenation level dependent (BOLD) signal used in functional magnetic resonance imaging (fMRI). In this paper the temporal and spatial statistical characteristics of fNIRSI data are compared to those of simultaneously acquired fMRI data in the human visual cortex during a variable-frequency reversing checkerboard activation paradigm. Changes in the size of activated volume caused by changes in checkerboard reversal frequency allowed a comparison of the behavior of the spatial responses measured by the two imaging methods. fNIRSI and fMRI data were each analyzed using standard correlation and fixed-effect group analyses of variance pathways. The statistical significance of fNIRSI data was found to be much lower than that of the fMRI data, due mainly to the low signal-to-noise of the measurements. Reconstructed images also showed that, while the time-course of changes in the oxy-, deoxy-, and total hemoglobin concentrations all exhibit high correlation with that of the BOLD response, the changes in the volume of tissue measured as "activated" by the BOLD response demonstrate a closer similarity to the corresponding changes in the oxy- and total hemoglobin concentrations than to that of the deoxyhemoglobin.

An integrated measurement system for simultaneous functional magnetic resonance imaging and diffuse optical tomography in human brain mapping.

An integrated measurement system is described for performing simultaneous functional magnetic resonance imaging (fMRI) and diffuse optical tomography (DOT) for human brain mapping experiments. The components of this system consist of an MRI-compatible multi-overlapping-channel optical probe, methods for co-registration of optical and fMRI measurements, and DOT reconstruction algorithms with structural and physiological constraints derived from the MRI data. The optical probe is fully MRI-compatible in the sense that it produces negligible MR image distortion and does not require any modification to the MRI scanner or data acquisition protocol. The probe can be attached to any part of the head without posing any limitation on optical data acquisition. Co-registration of images from fMRI and optical measurements was achieved by localizing the positions of the optical fibers using MRI markers. Human studies show successful implementation of the entire system.

Group Analysis of FMRI and NIR Data Simultaneously Acquired During Visual Stimulation in Humans.

We use our new combined functional near infrared spectro-imaging (fNIRSI) and magnetic resonance imaging (MRJ) technique to compare fMRI and fNIRSI data at different activation conditions, to obtain new information about the underlying physiology of the blood oxygen level dependent (BOLD) signal used in fMRI, and to assess statistical characteristics of spatial functional information provided by the group analysis of fNIRSI data. To achieve these goals we have acquired simultaneously fNIRSI and fMRI data during the presentation of the checkerboard reversing with different frequencies, and analyzed these data following the standard correlation and group analysis of variance pathway used in functional neuroimaging. . We have found that while the time courses of oxy-, deoxy-, and total- hemoglobin responses are equally well correlated with the time course of the BOLD response, the spatial pattern and magnitude of the BOLD response is better related to those of the oxy-, and total- hemoglobin responses rather than to the deoxyhemoglobin response. The statistical significance of the fNIRSI group maps is inferior to that of fMRI, and can be particularly compromised by the anatomical features of subjects.

Measurement of brain activity by near-infrared light.

We review our most recent results on near-IR studies of human brain activity, which have been evolving in two directions: detection of neuronal signals and measurements of functional hemodynamics. We discuss results obtained so far, describing in detail the techniques we developed for detecting neuronal activity, and presenting results of a study that, as we believe, confirms the feasibility of neuronal signal detection. We review our results on near-IR measurements of cerebral hemodynamics, which are performed simultaneously with functional magnetic resonance imaging (MRI) These results confirm the cerebral origin of hemodynamic signals measured by optical techniques on the surface of the head. We also show how near-IR methods can be used to study the underlying physiology of functional MRI signals.

Spatial and temporal hemodynamic study of human primary visual cortex using simultaneous functional MRI and diffuse optical tomography.

Blood oxygenation level dependent (BOLD) functional MRI and near infrared optical tomography have been widely used to investigate hemodynamic responses to functional stimulation in the human brain. In this paper, we present a complete methodology for integrating the two imaging modalities to study the underlying physiological mechanism of the hemodynamic response in primary visual cortex. Using a specially designed MRI-compatible optical probe, optical imaging was conducted using a frequency-domain near infrared spectrometer. Three-dimensional optical image reconstruction was based on diffuse optical tomography (DOT) using a perturbative approach. The sensitivity function of the forward problem was obtained using Monte Carlo simulations. From preliminary results, the spatial activation pattern of changes in deoxyhemoglobin concentration is consistent with the BOLD signal map. The patterns of oxy- and deoxyhemoglobin changes are also very similar to one another. The temporal hemodynamic response shows an increased total hemoglobin concentration, which indicates an increased cerebral blood volume (CBV) during physiological activation.

Simultaneous integrated diffuse optical tomography and functional magnetic resonance imaging of the human brain.

A complete methodology has been developed to integrate simultaneous diffuse optical tomography (DOT) and functional magnetic resonance imaging (MRI) measurements. This includes development of an MRI-compatible optical probe and a method for accurate estimation of the positions of the source and detector optodes in the presence of subject-specific geometric deformations of the optical probe. Subject-specific head models are generated by segmentation of structural MR images. DOT image reconstruction involves solution of the forward problem of light transport in the head using Monte Carlo simulations, and inversion of the linearized problem for small perturbations of the absorption coefficient. Initial results show good co-localization between the DOT images of changes in oxy- and deoxyhemoglobin concentration and functional MRI data.

Signal and image processing techniques for functional near-infrared imaging of the human brain.

Near-infrared spectro-imaging (NIRSI) is a quickly developing method for the in-vivo imaging of biological tissues. In particular, it is now extensively employed for imaging the human brain. In this non-invasive technique, the information about the brain is obtained from the analysis of spatial light bundles formed by the photons traveling from light sources to detectors placed on the surface of the head. Most significant problems in the functional brain NIRSI are the separation of the brain information from the physiological noise in non-cerebral tissues, and the localization of functional signals. In this paper we describe signal and image processing techniques we developed in order to measure two types of functional cerebral signals: the hemodynamic responses, and neuronal responses.

Near-infrared study of the underlying physiology of the functional magnetic resonance signal in humans during hypoxia.

We use near-infrared spectroscopy to investigate hemodynamic changes in humans during a breath holding exercise and their influence on the BOLD fMRI signal. We have quantitatively compared the BOLD fMRI signals with the hemoglobin concentration changes using correlation analysis of NIRS and fMRI data.