The use of near-infrared spectroscopy in understanding skeletal muscle physiology: recent developments

This article provides a snapshot of muscle near-infrared spectroscopy (NIRS) at the end of 2010 summarizing the recent literature, offering the present status and perspectives of the NIRS instrumentation and methods, describing the main NIRS studies on skeletal muscle physiology, posing open questions and outlining future directions. So far, different NIRS techniques (e.g. continuous-wave (CW) and spatially, time- and frequency-resolved spectroscopy) have been used for measuring muscle oxygenation during exercise. In the last four years, approximately 160 muscle NIRS articles have been published on different physiological aspects (primarily muscle oxygenation and haemodynamics) of several upper- and lower-limb muscle groups investigated by using mainly two-channel CW and spatially resolved spectroscopy commercial instruments. Unfortunately, in only 15 of these studies were the advantages of using multi-channel instruments exploited. There are still several open questions in the application of NIRS in muscle studies: (i)?whether NIRS can be used in subjects with a large fat layer; (ii) the contribution of myoglobin desaturation to the NIRS signal during exercise; (iii) the effect of scattering changes during exercise; and (iv) the effect of changes in skin perfusion, particularly during prolonged exercise. Recommendations for instrumentation advancements and future muscle NIRS studies are provided.     

Spatiotemporal properties of cortical haemodynamic response to auditory stimuli in sleeping infants revealed by multi-channel near-infrared spectroscopy

Multi-channel near-infrared spectroscopy (NIRS) has been used as a neuroimaging tool to study functional activation of the developing brain in infants. In this paper, we focus on spatiotemporal dynamics of cortical oxygenation changes during sensory processing in young infants. We use a 94-channel NIRS system to assess the activity of wide regions of the cortex in quietly sleeping three-month-old infants. Auditory stimuli composed of a random sequence of pure tones induced haemodynamic changes not only in the temporal auditory regions, but also in the occipital and frontal regions. Analyses of phase synchronization showed that mutual synchronizations of signal changes among the cortical regions were much stronger than the stimulus-induced synchronizations of signal changes. Furthermore, analyses of phase differences among cortical regions revealed phase advancement of the bilateral temporal auditory regions, and phase gradient in a posterior direction from the temporal auditory regions to the occipital regions and in an anterior direction within the frontal regions. We argue that multi-channel NIRS is capable of detecting the precise timing of cortical activation and its flow in the global network of the developing brain.     

Towards the next generation of near-infrared spectroscopy

Although near-infrared spectroscopy (NIRS) was originally designed for clinical monitoring of tissue oxygenation, it has also been developing into a useful tool for neuroimaging studies (functional NIRS). Over the past 30 years, technology has developed and NIRS has found a wide range of applications. However, the accuracy and reliability of NIRS have not yet been widely accepted, mainly because of the difficulties in selective and quantitative detection of signals arising in cerebral tissue, which subject the use of NIRS to a number of practical restrictions. This review summarizes the strengths and advantages of NIRS over other neuroimaging modalities and demonstrates specific examples. The issues of selective quantitative measurement of cerebral haemoglobin during brain activation are also discussed, together with the problems of applying the methods of functional magnetic resonance imaging data analysis to NIRS data analysis. Finally, near-infrared optical tomography--the next generation of NIRS--is described as a potential technique to overcome the limitations of NIRS.     

In-line reaction monitoring of a methyl methacrylate and N, N-dimethylacrylamide copolymerization reaction using near-infrared spectroscopy

Fast and accurate monitoring of monomer concentration during copolymerization reactions is of much interest. It is known that near-infrared spectroscopy (NIRS) can be used to monitor polymerization reactions. Here, a free radical solution copolymerization reaction between methyl methacrylate and N,N-dimethylacrylamide is considered. NIR spectra were measured in-line with a transflectance probe. The spectra of both involved monomers are very similar, making monitoring with NIRS challenging. It is shown that the NIRS calibration can be set up with only a few (5) off-line measured mixtures. Several validation methods for such a NIRS calibration model are discussed and tested. NIRS is used to follow conversion of the two monomers in a copolymerization reaction on-line.     

Monte Carlo study for physiological interference reduction in near-infrared spectroscopy based on empirical mode decomposition

Near-infrared spectroscopy (NIRS) can be used as the basis of non-invasive neuroimaging that may allow the measurement of haemodynamic changes in the human brain evoked by applied stimuli. Since this technique is very sensitive, physiological interference arising from the cardiac cycle and breathing can significantly affect the signal quality. Such interference is difficult to remove by conventional techniques because it occurs not only in the extracerebral layer but also in the brain tissue itself. Previous work on this problem employing temporal filtering, spatial filtering, and adaptive filtering have exhibited good performance for recovering brain activity data in evoked response studies. However, in this study, we present a time-frequency adaptive method for physiological interference reduction based on the combination of empirical mode decomposition (EMD) and Hilbert spectral analysis (HSA). Monte Carlo simulations based on a five-layered slab model of a human adult head were implemented to evaluate our methodology. We applied an EMD algorithm to decompose the NIRS time series derived from Monte Carlo simulations into a series of intrinsic mode functions (IMFs). In order to identify the IMFs associated with symmetric interference, the extracted components were then Hilbert transformed from which the instantaneous frequencies could be acquired. By reconstructing the NIRS signal by properly selecting IMFs, we determined that the evoked brain response is effectively filtered out with even higher signal-to-noise ratio (SNR). The results obtained demonstrated that EMD, combined with HSA, can effectively separate, identify and remove the contamination from the evoked brain response obtained with NIRS using a simple single source–detector pair.     

Shedding light on the adult brain: a review of the clinical applications of near-infrared spectroscopy

Near-infrared spectroscopy (NIRS) has potential as a non-invasive brain monitor in a wide range of clinical scenarios. In the last decade, there has been a rapid expansion of clinical experience using NIRS to monitor cerebral oxygenation, particularly in cardiac surgery, where there is some evidence that NIRS-guided brain protection protocols might lead to a reduction in peri-operative neurological complications. There are no data to support the wider application of NIRS to monitor cerebral oxygenation during routine anaesthesia and surgery, and its application in brain injury, where it might be expected to have a key monitoring role, is as yet undefined. Technological developments, including the introduction of broadband and time-resolved spectrometers that are capable of reliably measuring changes in oxidized cytochrome c oxidase, offer real potential for a single NIRS-based device to provide multi-site, regional monitoring of cerebral metabolic status as well as oxygenation and haemodynamics.     

The use of muscle near-infrared spectroscopy in sport, health and medical sciences: recent developments

Near-infrared spectroscopy (NIRS) has been shown to be one of the tools that can measure oxygenation in muscle and other tissues in vivo. This review paper highlights the progress, specifically in this decade, that has been made for evaluating skeletal muscle oxygenation and oxidative energy metabolism in sport, health and clinical sciences. Development of NIRS technologies has focused on improving quantification of the signal using multiple wavelengths to solve for absorption and scattering coefficients, multiple pathlengths to correct for the influence of superficial skin and fat, and time-resolved and phase-modulated light sources to determine optical pathlengths. In addition, advances in optical imaging with multiple source and detector pairs as well as portability using small wireless detectors have expanded the usefulness of the devices. NIRS measurements have provided information on oxidative metabolism in various athletes during localized exercise and whole-body exercise, as well as training-induced adaptations. Furthermore, NIRS technology has been used in the study of a number of chronic health conditions. Future developments of NIRS technology will include enhancing signal quantification. In addition, advances in NIRS imaging and portability promise to transform how measurements of oxygen utilization are obtained in the future.     

近红外光谱在药物领域的应用与研究进展

综述了近红外光谱技术在药物组分分析、药物物理表征和制药过程在线控制等方面的应用研究进 展.讨论了近红外光谱技术在我国制药工业中应用的前景.     

Application of near-infrared spectroscopy to optimize dissolution profiles of tablets according to the granulation mechanism

We developed a method for the optimization of dissolution properties of solid oral dosage forms manufacturing using high shear wet granulation (HSWG) by using near-infrared spectroscopy (NIRS) with chemometrics in small-scale experiments. The changes in rheology and NIR spectra of the granules were monitored to verify the granulation mechanism and determine the suitable water amount for model formulation during the HSWG. Tablets were manufactured by altering the added water amount to investigate the impact of the granulation mechanism on drug product qualities. Model formulation granules were prepared with 10–20% w/w water in a funicular state, corresponding to the plateau region in score plots obtained by principal component analysis (PCA). The dissolution rate of model formulation tablets manufactured with more than 20% w/w of water was significantly delayed while tablets manufactured with 15% w/w water showed 100% dissolution at 15?min. NIRS and PCA are applicable to the optimization of dissolution properties via the process understanding of HSWG at the early formulation development stage and could facilitate drug development.     

人血清中血糖的近红外光谱快速检测

应用傅利叶变换近红外光谱透射技术结合偏最小二乘法 ( PLS) ,快速定量分析了人血清中血糖含量 .利用内部交叉验证和自动优化功能对预测模型进行了优化 ,确定了最优建模参数 .模型对人血清中葡萄糖定标样品集的实测含量与预测含量的相关系数 r=0 .91 48,内部校正均方差 RMSECV=0 .487mmol/L.     

On-line monitoring of vacuum drying of theophylline using NIR spectroscopy: solid-state transitions,water content and semi-empirical modeling

The aim of this work was to monitor in-line and at a real time, the solid-state forms during pharmaceuticals manufacturing. It concerns the dehydration behavior and the solid-state transitions of theophylline in an agitated vacuum contact dryer. First, a near infrared spectroscopy (NIRS) method was performed using a reflectance diffuse probe to measure the in-line and in-situ exact composition of the mixture of different forms of theophylline and water content during drying. A multivariate modeling has been investigated to build a robust model which can predict four components at the same time during drying process. The XRPD analysis was used as a reference method in the process of calibration of NIRS. The indicators of the accuracy in quantitative spectral analysis confirm the robustness of the model and the efficiency of the method of calibration. Second, the kinetics of solid state transformations were investigated. It was shown that the dehydration advanced first by the formation of the metastable anhydrate and after a lag time of the stable one. Once the stable form appeared, formation of the metastable form came to an end. The temperature was found out to be the main factor controlling the overall process rate but also the final contents of the stable and metastable anhydrates for the considered dryer and operating conditions range. Finally, a semi-empirical drying model was proposed and significant quantitative differences were found, particularly at the product temperature which was probably caused by the excessive simplicity of the model.     

Noninvasive investigation of blood oxygenation dynamics of tumors by near-infrared spectroscopy

The measurement of dynamic changes in the blood oxygenation of tumor vasculature could be valuable for tumor prognosis and optimizing tumor treatment plans. In this study we employed near-infrared spectroscopy (NIRS) to measure changes in the total hemoglobin concentration together with the degree of hemoglobin oxygenation in the vascular bed of breast and prostate tumors implanted in rats. Measurements were made while inhaled gas was alternated between 33% oxygen and carbogen (95% O(2), 5% CO(2)). Significant dynamic changes in tumor oxygenation were observed to accompany respiratory challenge, and these changes could be modeled with two exponential components, yielding two time constants. Following the Fick principle, we derived a simplified model to relate the time constants to tumor blood-perfusion rates. This study demonstrates that the NIRS technology can provide an efficient, real-time, noninvasive means of monitoring the vascular oxygenation dynamics of tumors and facilitate investigations of tumor vascular perfusion. This may have prognostic value and promises insight into tumor vascular development.     

In vivo and noninvasive measurement of a songbird head's optical properties

By assessing the cerebral blood volume and the hemoglobin oxygen saturation level, near-infrared spectroscopy (NIRS) probes brain oxygenation, which reflects cerebral activity. To develop a noninvasive method monitoring the brain of a songbird, we use an original NIRS device, i.e., a white laser coupled with an ultrafast spectrotemporal detector of optical signals without wavelength scanning. We perform in vivo measurements of the absorption coefficient and the reduced scattering coefficient of the caudal nidopallium area of the head of a songbird (the zebra finch).     

A passenger reduces sleepy driver's activation in the right prefrontal cortex: A laboratory study using near-infrared spectroscopy

The present study aimed to examine how a passenger affects the sleepiness effect (awake vs. sleepy) on an individual's prefrontal activation during a simulated driving-game task using a wireless portable near-infrared spectroscopy (NIRS) device. Participants drove from start to goal along default routes either solely (no-passenger group) or with a friend sitting beside him/her as a passenger (with-passenger group). Sleepiness level was assessed by a five-item scale questionnaire. In the no-passenger group, there were no performance and activation differences between the sleepy and awake participants. In the with-passenger group, by contrast, the sleepy participants showed more errors and lower activations in their right prefrontal cortex than the awake participants. These results suggest that a passenger has little effect on awake participants, but may weaken the sleepy participants’ vigilance and/or their cognitive abilities of action control. Practically, the present study demonstrates that NIRS may provide us a new possibility to monitor and examine the driver's mental states in the brain.     

Noninvasive monitoring of estrogen effects against ischemic stroke in rats by near-infrared spectroscopy

The aim of this study was to assess hemodynamic changes by near-infrared spectroscopy (NIRS) during acute focal cerebral ischemia and reperfusion. The study also has evaluated the therapeutic effects of estrogen against vascular dysfunction. Focal cerebral ischemia was induced in nine bilaterally ovariectomized rats, using an endovascular occlusion technique of the middle cerebral artery (MCA). Four out of nine rats had estrogen pretreatment before MCA occlusion (MCAO). The other five rats had MCAO with no pretreatment. The occlusion time was 60 min, followed by 40-60 min of reperfusion. Real-time monitoring of changes in hemoglobin concentrations was performed by a steady-state, two-channel, NIRS system through the period of occlusion and reperfusion. Both changes in total and oxygenated hemoglobin concentrations (D[HbT] and D[HbO(2)]) display apparent periodic fluctuations during occlusion for the rats without estrogen pretreatment, while no rhythmic fluctuation was observed in the rats with the pretreatment. This rhythmic fluctuation is a microvascular dysfunction. Fourier power spectral analysis was performed on the D[HbO(2)] profiles in both rat groups. The results show that the cumulative frequency power of D[HbO(2)] in the range of 0.0025-0.01 Hz for the rats without pretreatment is significantly higher than that with pretreatment. The study implies that the dysfunctional fluctuations disappear in the rats with estrogen pretreatment, demonstrating a new application of NIRS, i.e., to detect focal cerebral ischemia and to monitor cerebral responses to therapy against vascular dysfunction in animal models.     

Near-infrared light propagation in an adult head model. II. Effect of superficial tissue thickness on the sensitivity of the near-infrared spectroscopy signal

It is important for near-infrared spectroscopy (NIRS) and imaging to estimate the sensitivity of the detected signal to the change in hemoglobin that results from brain activation and the volume of tissue interrogated for a specific source-detector fiber spacing. In this study light propagation in adult head models is predicted by Monte Carlo simulation to investigate the effect of the superficial tissue thickness on the partial optical path length in the brain and on the spatial sensitivity profile. In the case of source-detector spacing of 30 mm, the partial optical path length depends mainly on the depth of the inner skull surface whereas the spatial sensitivity profile is significantly affected by the thickness of the cerebrospinal fluid layer. The mean optical path length that can be measured by time-resolved experiments increases when the skull thickness increases whereas the partial mean optical path length in the brain decreases when the skull thickness increases. These results indicate that it is not appropriate to use the mean optical path length as an alternative to the partial optical path length to compensate the NIRS signal for the difference in sensitivity caused by variation of the superficial tissue thickness.     

Quantifying low amorphous or crystalline amounts of alpha-lactose-monohydrate using X-ray powder diffraction, near-infrared spectroscopy, and differential scanning calorimetry

Efficient and accurate quantification of low amorphous and crystalline contents within pharmaceutical materials still remains a challenging task in the pharmaceutical industry. Since X-ray powder diffraction (XRPD) equipment has improved in recent years, our aim was 1) to investigate the possibility of substantially lowering the detection limits of amorphous or crystalline material to about 1% or 0.5% w/w respectively by applying conventional Bragg Brentano optics, combined with a fast and simple evaluation technique; 2) to perform these measurements within a short time to make it suitable for routine analysis; and 3) to subject the same data sets to a partial least squares regression (PLSR) in order to investigate whether it is possible to improve accuracy and precision compared to the standard integration method. Near-infrared spectroscopy (NIRS) and differential scanning calorimetry (DSC) were chosen as reference method. As model substance, alpha lactose monohydrate was chosen to create calibration curves based on predetermined mixtures of highly crystalline and amorphous substance. In contrast to DSC, XRPD and NIRS revealed an excellent linearity, precision, and accuracy with the percent of crystalline amount and a detectability down to about 0.5% w/w. Chemometric evaluation (partial least squares regression) applied to the XRPD data further improved the quality of our calibration.     

Excitation saturation in two-photon fluorescence correlation spectroscopy

Fluorescence correlation spectroscopy (FCS) has become a powerful and sensitive research tool for the study of molecular dynamics at the single-molecule level. Because photophysical dynamics often dramatically influence FCS measurements, the role of various photophysical processes in FCS measurements must be understood to accurately interpret FCS data. We describe the role of excitation saturation in two-photon fluorescence correlation measurements. We introduce a physical model that characterizes the effects of excitation saturation on the size and shape of the two-photon fluorescence observation volume and derive a new analytical expression for fluorescence correlation functions that includes the influence of saturation. With this model, we can accurately describe both the temporal decay and the amplitude of measured fluorescence correlation functions over a wide range of illumination powers.     

The use of near-infrared spectroscopy for the quantitation of a drug in hot-melt extruded films

The objective of the study was to demonstrate the utility of near-infrared spectroscopy (NIRS) for quantitative analysis of a model drug in hot-melt extruded film formulations. Polyethylene oxide (PEO) films with clotrimazole (CT) as a model drug were prepared by hot-melt extrusion (HME) incorporating drug concentrations ranging from 0-20% and analyzed using a Fourier transform near-infrared (FT-NIR) spectrophotometer in the reflectance mode. High performance liquid chromatography (HPLC) was the reference method used for this study. The NIR calibration model derived for CT was composed of 21 frequency ranges that were correlated to the values quantified using the HPLC reference method. The NIR method developed resulted in an assayed CT amount in the film matrix to be within 3.5% of the quantity determined by the reference method. These studies clearly demonstrate that NIRS is a powerful method for the quantitation of active drug substances contained in films produced by HME and warrants further investigation.     

Has the time come to use near-infrared spectroscopy as a routine clinical tool in preterm infants undergoing intensive care?

Several instruments implementing spatially resolved near-infrared spectroscopy (NIRS) to monitor tissue oxygenation are now approved for clinical use. The neonatal brain is readily assessible by NIRS and neurodevelopmental impairment is common in children who were in need of intensive care during the neonatal period. It is likely that an important part of the burden of this handicap is due to brain injury induced by hypoxia-ischaemia during intensive care. In particular, this is true for infants born extremely preterm. Thus, monitoring of cerebral oxygenation has considerable potential benefit in this group. The benefit, however, should be weighed against the disturbance to the infant, against the limitations imposed on clinical care and against costs. The ultimate way of demonstrating the 'added value' is by a randomized controlled trial. Cerebral oximetry must reduce the risk of a clinically relevant endpoint, such as death or neurodevelopmental handicap. We estimate that such a trial should recruit about 4000 infants to have the power to detect a reduction in brain injury by one-fifth. This illustrates the formidable task of providing first-grade evidence for the clinical value of diagnostic methods. Is it a window of opportunity for the establishment of a rational basis before another technology is added to an already overly complex newborn intensive care?