The utility of far‐infrared illumination in oxygenation dynamics as measured with near‐infrared spectroscopy

Near‐infrared spectroscopy (NIRS) is a noninvasive method for measuring the oxygenation in muscle and other tissues in vivo. For quantitative NIRS measurement of oxygenation dynamics, the vessel‐occlusion test was usually applied as physiological intervention. There are several drawbacks of the vessel‐occlusion method that include skin contact, uncomfortable and microcirculation block of patients. Thus, we propose the far‐infrared (FIR) illumination as a new physiological intervention method in this paper. Our preliminary result shows a linear correlation of oxygenation dynamic signals between FIR illumination and arterial‐occlusion test (AOT) that implies the FIR illumination could be applied for hemodynamic response measurement in clinical diagnosis. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Optimization of extracorporeal membrane oxygenation therapy using near‐infrared spectroscopy to assess changes in peripheral circulation: A pilot study

Near‐infrared spectroscopy (NIRS) has been proposed as a noninvasive modality for detecting complications in patients undergoing extracorporeal membrane oxygenation (ECMO), and it can simultaneously reveal the global circulatory status of these patients. We optimized ECMO therapy on the basis of real‐time peripheral NIRS probing. Three patients underwent venoarterial (VA) ECMO and one patient underwent venovenous (VV) ECMO. All patients received peripheral ECMO cannulation with routine distal perfusion catheter placement. We designed an experimental protocol to adjust ECMO blood flow over 1 hour. Hemodynamic responses were measured using NIRS devices attached to the calf at approximately 60% of the distance from the ankle to the knee. HbO₂ levels change substantially with adjustments in ECMO flow, and they are more sensitive than HHb levels and the tissue saturation index (TSI) are. NIRS for optimizing ECMO therapy may be reliable for monitoring global circulatory status.     

Oxygenation dynamics of sepsis patients undergoing far‐infrared intervention based on near‐infrared spectroscopy

Near‐infrared spectroscopy (NIRS; continuous wave type) is a noninvasive tool for detecting the relative change of oxyhemoglobin and deoxyhemoglobin. To make this change, intervention methods must be applied. This study determined the hemodynamics of 44 healthy participants and 35 patients with sepsis during exposure to FIR as a novel physical intervention approach. Local microcirculation of their brachioradialis was monitored during exposure and recovery through NIRS. The variations in blood flow and microvascular reaction were determined by conducting paired and unpaired t tests. The oxyhemoglobin levels of the healthy participants increased continuously, even during recovery. In contrast to expextations, the oxyhemoglobin levels of the patients plateaued after only 5 min of FIR illumination. The proposed method has potential applications for ensuring efficient treatment and facilitating doctors in diagnosing the functions of vessels in intensive care units.

Mapping diagrams of HbO₂ in healthy males and males with sepsis illustrated unique scenarios during the process.     

Functional near infrared spectroscopy using spatially resolved data to account for tissue scattering: A numerical study and arm‐cuff experiment

Functional Near‐Infrared Spectroscopy (fNIRS) aims to recover changes in tissue optical parameters relating to tissue hemodynamics, to infer functional information in biological tissue. A widely‐used application of fNIRS relies on continuous wave (CW) methodology that utilizes multiple distance measurements on human head for study of brain health. The typical method used is spatially resolved spectroscopy (SRS), which is shown to recover tissue oxygenation index (TOI) based on gradient of light intensity measured between two detectors. However, this methodology does not account for tissue scattering which is often assumed. A new parameter recovery algorithm is developed, which directly recovers both the scattering parameter and scaled chromophore concentrations and hence TOI from the measured gradient of light‐attenuation at multiple wavelengths. It is shown through simulations that in comparison to conventional SRS which estimates cerebral TOI values with an error of ±12.3%, the proposed method provides more accurate estimate of TOI exhibiting an error of ±5.7% without any prior assumptions of tissue scatter, and can be easily implemented within CW fNIRS systems. Using an arm‐cuff experiment, the obtained TOI using the proposed method is shown to provide a higher and more realistic value as compared to utilizing any prior assumptions of tissue scatter.     

Altered near‐infrared spectroscopy response to breath‐holding in patients with fibromyalgia

Fibromyalgia (FM) is a complex syndrome characterized by chronic widespread pain and a heightened response to pressure. Most medical researches pointed out that FM patients with endothelial dysfunction and arterial stiffness. A continuous‐wave near‐infrared spectroscopy (NIRS) system is used in present study to measure the hemodynamic changes elicited by breath‐holding task in patients with FM. Each patient completed a questionnaire survey including demographics, characteristics of body pain, associated symptoms, headache profiles and Hospital Anxiety and Depression Scale. A total of 27 FM patients and 26 health controls were enrolled. In comparison with healthy controls, patients with FM showed lower maximal and averaged change of oxyhemoglobin concentration in both the left (1.634 ±0.890 and 0.810 ±0.525 μM) and the right (1.576 ±0.897 and 0.811 ±0.601 μM) prefrontal cortex than healthy controls (P < .05 for both sides) during the breath‐holding task. In conclusion, FM is associated with altered cerebrovascular reactivity measured by NIRS and breath‐holding task, which may reflect endothelial dysfunction or arterial stiffness. Oxygenated hemoglobin concentration changes of healthy controls and FM patients.      

Gender differences in brain networks during verbal Sternberg tasks: A simultaneous near‐infrared spectroscopy and electro‐encephalography study

Gender differences in psychological processes have been of great interest in a variety of fields including verbal fluency, emotion processing and working memory. Previous studies suggested that women outperform men in verbal working memory (VWM). However, the inherent mechanisms are still unclear. To obtain a deeper insight into the gender differences in brain networks in VWM, this study used near‐infrared spectroscopy (NIRS) and electro‐encephalography (EEG) simultaneously to investigate gender‐related brain networks during verbal Sternberg tasks. NIRS results confirmed that women surpass men in VWM from the perspective of both brain activation and connectivity. Results of EEG (effective connectivity and event‐related spectral power) showed that men tend to use a more visuospatial strategy to encode memory. In addition, novel analysis methods of brain networks can provide useful information about the gender specifics of brain functions. Gender‐related pseudo‐color maps constructed from all channels of average HbO₂ activity during low‐ and high‐load tasks (from 0 to 6 seconds after beginning).      

Phase dual‐slopes in frequency‐domain near‐infrared spectroscopy for enhanced sensitivity to brain tissue: First applications to human subjects

We present a first in vivo application of phase dual‐slopes (DS?), measured with frequency‐domain near‐infrared spectroscopy on four healthy human subjects, to demonstrate their enhanced sensitivity to cerebral hemodynamics. During arterial blood pressure oscillations elicited at a frequency of 0.1 Hz, we compare three different ways to analyze either intensity (I) or phase (?) data collected on the subject's forehead at multiple source‐detector distances: Single‐distance, single‐slope and DS. Theoretical calculations based on diffusion theory show that the method with the deepest maximal sensitivity (at about 11 mm) is DS?. The in vivo results indicate a qualitative difference of phase data (especially DS?) and intensity data (especially single‐distance intensity [SDI]), which we assign to stronger contributions from scalp hemodynamics to SDI and from cortical hemodynamics to DS?. Our findings suggest that scalp hemodynamic oscillations may be dominated by blood volume dynamics, whereas cortical hemodynamics may be dominated by blood flow velocity dynamics.     

In‐situ monitoring of Saccharomyces cerevisiae ITV01 bioethanol process using near‐infrared spectroscopy NIRS and chemometrics

The application feasibility of in‐situ or in‐line monitoring of S. cerevisiae ITV01 alcoholic fermentation process, employing Near‐Infrared Spectroscopy (NIRS) and Chemometrics, was investigated. During the process in a bioreactor, in the complex analytical matrix, biomass, glucose, ethanol and glycerol determinations were performed by a transflection fiber optic probe immersed in the culture broth and connected to a Near‐Infrared (NIR) process analyzer. The NIR spectra recorded between 800 and 2,200 nm were pretreated using Savitzky‐Golay smoothing and second derivative in order to perform a partial least squares regression (PLSR) and generate the calibration models. These calibration models were tested by external validation and then used to predict concentrations in batch alcoholic fermentations. The standard errors of calibration (SEC) for biomass, ethanol, glucose and glycerol were 0.212, 0.287, 0.532, and 0.296 g/L and standard errors of prediction (SEP) were 0.323, 0.369, 0.794, and 0.507 g/L, respectively. Calibration and validation criteria were defined and evaluated in order to generate robust and reliable models for an alcoholic fermentation process matrix. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:510–517, 2016     

Real‐time monitoring prefrontal activities during online video game playing by functional near‐infrared spectroscopy

A growing body of literature has suggested that video game playing can induce functional and structural plasticity of the brain. The underlying mechanisms, however, remain poorly understood. In this study, functional near‐infrared spectroscopy (fNIRS) was used to record prefrontal activities in 24 experienced game players when they played a massively multiplayer online battle arena video game, League of Legends (LOL), under naturalistic conditions. It was observed that game onset was associated with significant activations in the ventrolateral prefrontal cortex (VLPFC) and concomitant deactivations in the dorsolateral prefrontal cortex (DLPFC) and frontal pole area (FPA). Game events, such as slaying an enemy and being slain by an enemy evoked region‐specific time‐locked hemodynamic/oxygenation responses in the prefrontal cortex (PFC). It was proposed that the VLPFC activities during LOL playing are likely responses to visuo‐motor task load of the game, while the DLPFC/FPA activities may be involved in the constant shifts of attentional states and allocation of cognitive resources required by game playing. The present study demonstrated that it is feasible to use fNIRS to monitor real‐time prefrontal activity during online video game playing.      

The whither of bacteriophytochrome‐based near‐infrared fluorescent proteins: Insights from two‐photon absorption spectroscopy

We present one‐ and two‐photon‐absorption fluorescence spectroscopic analysis of biliverdin (BV) chromophore–based single‐domain near‐infrared fluorescent proteins (iRFPs). The results of these studies are used to estimate the internal electric fields acting on BV inside iRFPs and quantify the electric dipole properties of this chromophore, defining the red shift of excitation and emission spectra of BV‐based iRFPs. The iRFP studied in this work is shown to fit well the global diagram of the red‐shift tunability of currently available BV‐based iRFPs as dictated by the quadratic Stark effect, suggesting the existence of the lower bound for the strongest red shifts attainable within this family of fluorescent proteins. The absolute value of the two‐photon absorption (TPA) cross section of a fluorescent calcium sensor based on the studied iRFP is found to be significantly larger than the TPA cross sections of other widely used genetically encodable fluorescent calcium sensors.      

Brain structure and spatial sensitivity profile assessing by near‐infrared spectroscopy modeling based on 3D MRI data

The goal of this study is to prove that the light propagation in the head by used the 3‐D optical model from in vivo MRI data set can also provide significant characteristics on the spatial sensitivity of cerebral cortex folding geometry based on Monte Carlo simulation. Thus, we proposed a MRI based approach for 3‐D brain modeling of near‐infrared spectroscopy (NIRS). In the results, the spatial sensitivity profile of the cerebral cortex folding geometry and the arrangement of source‐detector separation have being necessarily considered for applications of functional NIRS. The optimal choice of source‐detector separation is suggested within 3–3.5 cm by the received intensity with different source‐detector separations and the ratio of received light from the gray and white matter layer is greater than 50%. Additionally, this study has demonstrated the capability of NIRS in not only assessing the functional but also detecting the structural change of the brain by taking advantage of the low scattering and absorption coefficients observed in CSF of sagittal view. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Advanced near‐infrared monitor for stable real‐time measurement and control of Pichia pastoris bioprocesses

Near‐infrared spectroscopy is considered to be one of the most promising spectroscopic techniques for upstream bioprocess monitoring and control. Traditionally the nature of near‐infrared spectroscopy has demanded multivariate calibration models to relate spectral variance to analyte concentrations. The resulting analytical measurements have proven unreliable for the measurement of metabolic substrates for bioprocess batches performed outside the calibration process. This paper presents results of an innovative near‐infrared spectroscopic monitor designed to follow the concentrations of glycerol and methanol, as well as biomass, in real time and continuously during the production of a monoclonal antibody by a Pichia pastoris high cell density process. A solid state instrumental design overcomes the ruggedness limitations of conventional interferometer‐based spectrometers. Accurate monitoring of glycerol, methanol, and biomass is demonstrated over 274 days postcalibration. In addition, the first example of feedback control to maintain constant methanol concentrations, as low as 1 g/L, is presented. Postcalibration measurements over a 9‐month period illustrate a level of reliability and robustness that promises its adoption for online bioprocess monitoring throughout product development, from early laboratory research and development to pilot and manufacturing scale operation. © 2014 American Institute of Chemical Engineers Biotechnol. Prog., 30:749–759, 2014     

Race‐specific differences in the phase coherence between blood flow and oxygenation: A simultaneous NIRS,white light spectroscopy and LDF study

Race‐specific differences in the level of glycated hemoglobin are well known. However, these differences were detected by invasive measurement of mean oxygenation, and their understanding remains far from complete. Given that oxygen is delivered to the cells by hemoglobin through the cardiovascular system, a possible approach is to investigate the phase coherence between blood flow and oxygen transportation. Here we introduce a noninvasive optical method based on simultaneous recordings using NIRS, white light spectroscopy and LDF, combined with wavelet‐based phase coherence analysis. Signals were recorded simultaneously for individuals in two groups of healthy subjects, 16 from Sub‐Saharan Africa (BA group) and 16 Europeans (CA group). It was found that the power of myogenic oscillations in oxygenated and de‐oxygenated hemoglobin is higher in the BA group, but that the phase coherence between blood flow and oxygen saturation, or blood flow and hemoglobin concentrations is higher in the CA group     

Transmission in near‐infrared optical windows for deep brain imaging

Near‐infrared (NIR) radiation has been employed using one‐ and two‐photon excitation of fluorescence imaging at wavelengths 650–950 nm (optical window I) for deep brain imaging; however, longer wavelengths in NIR have been overlooked due to a lack of suitable NIR‐low band gap semiconductor imaging detectors and/or femtosecond laser sources. This research introduces three new optical windows in NIR and demonstrates their potential for deep brain tissue imaging. The transmittances are measured in rat brain tissue in the second (II, 1,100–1,350 nm), third (III, 1,600–1,870 nm), and fourth (IV, centered at 2,200 nm) NIR optical tissue windows. The relationship between transmission and tissue thickness is measured and compared with the theory. Due to a reduction in scattering and minimal absorption, window III is shown to be the best for deep brain imaging, and windows II and IV show similar but better potential for deep imaging than window I.

     

Model study of time‐dependent muscle response to pulsed electrical stimulation

A systems‐level model analysis of neuromuscular response to external electrical stimulation is presented. Action potential (AP) generation, dynamics of voltage‐based calcium release at the motor endplates controlled by the arrival of APs, and muscle force production are all comprehensively included. Numerical predictions exhibit trends that are qualitatively similar to measurements of muscle response in rats from a burst of cortical stimulation and a nanosecond impulse. Modulation of neural membrane conductances (including possible electroporation) that alters the neural impulse generation frequency is hypothesized as a possible mechanism leading to observed changes in muscle force production. Other possibilities such as calcium release at nerve end endings also exist. It is also proposed that multipulsing strategies and changing the electric field direction by using multielectrode systems would be useful. Bioelectromagnetics 31:361–370, 2010. © 2010 Wiley‐Liss, Inc.     

Computed tomography for in vivo deep over‐1000 nm near‐infrared fluorescence imaging

This study aims to develop a novel cross‐sectional imaging of fluorescence in over‐1000 nm near‐infrared (OTN‐NIR), which allows in vivo deep imaging, using computed tomography (CT) system. Cylindrical specimens of composite of OTN‐NIR fluorophore, NaGdF₄ co‐doped with Yb³⁺ and Ho³⁺ (ex: 980 nm, em: 1150 nm), were embedded in cubic agar (10.5–12 mm) or in the peritoneal cavity of mice and placed on a rotatable stage. When the fluorescence from inside of the samples was serially captured from multiple angles, the images were disrupted by the reflection and refraction of emitted light on the sample‐air interface. Immersing the sample into water filled in a rectangular bath suppressed the disruption at the interface and successfully reconstructed the position and concentration of OTN‐NIR fluorophores on the cross‐sectional images using a CT technique. This is promising as a novel three‐dimensional imaging technique for OTN‐NIR fluorescent image projections of small animals captured from multiple angles.     

Controlling the near‐infrared transparency of costal cartilage by impregnation with clearing agents and magnetite nanoparticles

Penetration depth of near‐infrared laser radiation to costal cartilage is controlled by the tissue absorption and scattering, and it is the critical parameter to provide the relaxation of mechanical stress throughout the whole thickness of cartilage implant. To enhance the penetration for the laser radiation on 1.56 μm, the optical clearing solutions of glycerol and fructose of various concentrations are tested. The effective and reversible tissue clearance was achieved. However, the increasing absorption of radiation should be concerned: 5°C‐8°C increase of tissue temperature was detected. Laser parameters used for stress relaxation in cartilage should be optimized when applying optical clearing agents. To concentrate the absorption in the superficial tissue layers, magnetite nanoparticle (NP) dispersions with the mean size 95 ± 5 nm and concentration 3.9 ± 1.1 × 10¹¹ particles/mL are applied. The significant increase in the tissue heating rate was observed along with the decrease in its transparency. Using NPs the respective laser power can be decreased, allowing us to obtain the working temperature locally with reduced thermal effect on the surrounding tissue.      

Optimal imaging windows of indocyanine green‐assisted near‐infrared dental imaging with rat model and its comparison to X‐ray imaging

In this study, we used rat animal model to compare the efficiency of indocyanine green (ICG)‐assisted dental near‐infrared fluorescence imaging with X‐ray imaging, and we optimized the imaging window for both unerupted and erupted molars. The results show that the morphology of the dental structures was observed clearly from ICG‐assisted dental images (especially through the endoscope). A better image contrast was easily acquired at the short imaging windows (<10 minutes) for unerupted and erupted molars. For unerupted molars, there is another optimized imaging window (48‐96 hours) with a prominent glow‐in‐the‐dark effect: only the molars remain bright. This study also revealed that the laser ablation of dental follicles can disrupt the molar development, and our method is able to efficiently detect laser‐treated molars and acquire the precise morphology. Thus, ICG‐assisted dental imaging has the potential to be a safer and more efficient imaging modality for the real‐time diagnosis of dental diseases.     

Near‐infrared bone densitometry: A feasibility study on distal radius measurement

Osteoporosis, defined as decreased bone mineral density (BMD), poses patients in dangers for fracture risk and has become a major public health problem worldwide because of is associated morbidity, mortality and costs. Without doubt, early detection and timely intervention are important to successfully manage osteoporosis and its associated complications. The dual‐energy x‐ray absorptiometry (DXA) is the most popular and standard method to measure BMD. However, limitations including radiation exposure and availability restrict its application for osteoporosis screening among general population. In this study, we developed a simple method to detect human distal radius bone density based on near infrared (NIR) image system. Among 10 volunteers (including 5 young and 5 elderly participants) receiving bone density measurement using our NIR image system at the ultradistal part of bilateral distal radius, we demonstrated a strong correlation between the optical attenuation and BMD measured with DXA, which may facilitate predicting bone density status. We hope our potential NIR image system may open a new avenue for development of osteoporosis screening facilities and help in prevention of osteoporosis related fracture and its associated complications in the near future. Pearson's correlations between BMD values from the DXA and light intensity of NIR system.