Influence of hypoxia on wavelength dependence of differential pathlength and near-infrared quantification

Continuous wave near-infrared spectroscopy (NIRS) measurements of cardiac correlated changes in attenuation in the adult human head were computed using a Fourier analysis technique that eliminates the positive error bias associated with the magnitude of the Fourier coefficient. These attenuation changes were used to determine wavelength dependence of differential pathlength, DP(lambda), at four stages during progressive hypoxia (21, 17, 13 and 9% FIO2) in normal volunteers. The effects of incorporating DP(lambda) into NIRS algorithms to compute relative concentration changes and absolute concentration of oxyhaemoglobin and deoxyhaemoglobin are discussed. Because variations in DP(lambda) are restricted to wavelengths below 780 nm, absolute concentration calculations are influenced by hypoxia-induced changes while relative concentrations are unaffected. However, even accounting for changes in DP(lambda) did not allow computation of physiologically reasonable absolute concentrations of the haemoglobin species.     

A noninvasive multimodal technique to monitor brain tumor vascularization

Determination of tumor oxygenation at the microvascular level will provide important insight into tumor growth, angiogenesis, necrosis and therapeutic response and will facilitate to develop protocols for studying tumor behavior. The non-ionizing near infrared spectroscopy (NIRS) technique has the potential to differentiate lesion and hemoglobin dynamics; however, it has a limited spatial resolution. On the other hand, magnetic resonance imaging (MRI) has achieved high spatial resolution with excellent tissue discrimination but is more susceptible to limited ability to monitor the hemoglobin dynamics. In the present work, the vascular status and the pathophysiological changes that occur during tumor vascularization are studied in an orthotopic brain tumor model. A noninvasive multimodal approach based on the NIRS technique, namely steady state diffuse optical spectroscopy (SSDOS) along with MRI, is applied for monitoring the concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor region. The concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor vasculature are extracted at 15 discrete wavelengths in a spectral window of 675-780 nm. We found a direct correlation between tumor size, intratumoral microvessel density and tumor oxygenation. The relative decrease in tumor oxygenation with growth indicates that though blood vessels infiltrate and proliferate the tumor region, a hypoxic trend is clearly present.     

Spatial sensitivity of acousto-optic and optical near-infrared spectroscopy sensing measurements

Near-infrared spectroscopy (NIRS) is a popular sensing technique to measure tissue oxygenation noninvasively. However, the region of interest (ROI) is often beneath a superficial layer, which affects its accuracy. By applying focused ultrasound in the ROI, acousto-optic (AO) techniques can potentially minimize the effect of physiological changes in the superficial layer. Using absorption perturbation experiments in both transmission and reflection modes, we investigated the spatial sensitivity distributions and mean penetration depths of an AO system based on a digital correlator and two popular NIRS systems based on i. intensity measurements using a single source and detector configuration, and ii. spatially resolved spectroscopy. Our results show that for both transmission and reflection modes, the peak relative sensitivities of the two NIRS systems are near to the superficial regions, whereas those of the AO technique are near to the ROIs. In the reflection mode, when the ROI is deeper than 14 mm, the AO technique has a higher absolute mean sensitivity than the two NIRS techniques. As the focused ultrasound is moved deeper into the turbid medium, the mean penetration depth increases accordingly. The focused ultrasound can shift the peak relative sensitivity of the AO measurement toward its focused region.     

近红外光谱技术在临床检测中的应用

近红外光谱（near infrared spectroscopy,NIRS）分析技术是近年来发展最快、最引人注目的 分析技术,广泛应用于石油、化工、食品等分析化学各领域.本文在介绍NIRS技术基本原理、技术特点的基础上,阐述了NIRS技术在临床检测领域的研究情况,主要包括在无创血糖监测、无创血氧测量、乳腺肿块检测、尿液成分分析等方面的应用与进展,最后初步探讨了该技术在应用中存在的局限性,并对NIRS分析技术在临床检测领域中的应用前景进行了展望.     

Effect of hemolysis on oxygen and hematocrit measurements by near infrared reflectance spectroscopy

A short review of the principles of near infrared reflectance spectroscopy (NIRS) in whole blood is followed by a discussion on the influence of hemolysis. The increase of free plasmahemoglobin (PHb) has a strong influence on the continuous measurement of hematocrit and oxygen saturation (O(2)S) by NIRS. In view of the relative stability of hematocrit values in vivo this effect may be used to detect a change of the hemolysis rate induced by blood pumps in case of malfunction.The aim of this study is, therefore, the assessment of the hemolysis rate within an in vitro mock loop comprising a rotary blood pump by means of NIRS at constant hematocrit levels compared to the photometric reference method. Reflected light is measured by an integrated optical sensor working at three wavelengths (660 nm, 730 nm, and 830 nm). The experimental results demonstrate that the increase of free hemoglobin in plasma due to mechanical pumping leads to a decrease of detected reflected light at all three wavelengths. Influencing parameters such as adhering proteins on the sensor surface and the blood flow rate are briefly discussed. Finally, the possibility of using NIRS sensors for detecting malfunctions of blood pumps in vitro and in vivo is discussed, together with the option of using these sensors for supervision of long-term implantable pumps.     

An evaluation of near infrared spectroscopy and cryospectrophotometry estimates of haemoglobin oxygen saturation in a rodent mammary tumour model

Haemoglobin oxygen saturation in subcutaneous rat mammary tumours was measured using near infrared spectroscopy (NIRS) in vivo and in rapidly frozen sections from the same tumours using cryospectrophotometry, which reports oxygen saturation in individual blood vessels to depths of 4 mm from the tissue surface. Measurements were performed on tumours while animals breathed either room air or carbogen. In five of nine tumours, the average saturation calculated from cryospectrophotometric measurements agreed with that determined from NIRS to within 13%, and in four of these five tumours agreement was 5% or better. In the remaining four of nine tumours, where agreement was poor, the volume-averaged saturations estimated from NIRS were consistently higher than those calculated from cryospectrophotometry. Monte Carlo simulations demonstrated that the depth of tissue probed by NIRS was significantly greater than that sampled by cryospectrophotometry. Analysis of the frequency of severely hypoxic vessels showed that when NIRS reported a saturation of approximately 70% or higher, the fraction of tumour vessels with saturations less than 10% was limited to 0.06 or less. Sensitivity and specificity analysis suggests that NIRS and NIRS imaging may identify clinically relevant hypoxia, even when its spatial extent is below the resolution limit of the NIRS technique.     

Measurement of venous oxyhaemoglobin saturation in the adult human forearm by near infrared spectroscopy with venous occlusion

Measurement of the oxygenation of the peripheral tissues provides useful information about tissue perfusion. A method is described for the measurement of peripheral venous oxyhaemaglobin saturation (SvO₂) in the adult forearm by a non-invasive technique, near infrared spectroscopy (NIRS) with venous occlusion. A series of studies is performed on healthy adults to compare measurements of forearm SvO₂ made by NIRS with measurements of superficial venous SvO₂ made by co-oximetry, and to study the effect of different optode spacings. There is a significant correlation between forearm SvO₂ measured by NIRS and SvO₂ of superficial venous blood measured by cooximetry (n=19, r=0.7, p<0.0001). Higher values for SvO₂ were obtained using a 2.5 cm spacing than with a 4 cm spacing (mean difference=4.1% (95% Cl 1.4%–6.8%) n=16). This difference is likely to have been due to a more superficial volume of tissue being studied with the closer optode spacing. Peripheral SvO₂ can be measured non-invasively using NIRS with venous occlusion. It may prove to be a useful method to study circulatory disturbances.     

脑组织血管动态调节的无损伤测量研究

近红外光谱信号分析 (NIRS)近年来发展迅速并获得临床应用 ,人们一直试图用此方法得到精确的组织血液成分的信息 ,而没有挖掘其中蕴涵的血管动态调节的丰富信息。本文描述了一种新的近红外光谱信号分析方法 (NIRS) ,能区分出动脉血和静脉血的相对变化 ,实现脑组织血管动态调节的无损伤测量。通过设计一些可用已知生理学理论解析的方法诱发组织血管的调节作用 ,对比观察电磁血流量计和NIRS测量结果 ,并进行了人体实测研究。目的在于使由此而得到的血管调节信息易于判断与确信 ,从而有利于运用这种连续动态的光电检测法去观察更深层的生理与心理的未知现象。     

Noninvasive optical quantification of absolute blood flow, blood oxygenation, and oxygen consumption rate in exercising skeletal muscle

This study investigates a method using novel hybrid diffuse optical spectroscopies [near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS)] to obtain continuous, noninvasive measurement of absolute blood flow (BF), blood oxygenation, and oxygen consumption rate (V?O(2)) in exercising skeletal muscle. Healthy subjects (n=9) performed a handgrip exercise to increase BF and V?O(2) in forearm flexor muscles, while a hybrid optical probe on the skin surface directly monitored oxy-, deoxy-, and total hemoglobin concentrations ([HbO(2)], [Hb], and THC), tissue oxygen saturation (S(t)O(2)), relative BF (rBF), and relative oxygen consumption rate (rV?O(2)). The rBF and rV?O(2) signals were calibrated with absolute baseline BF and V?O(2) obtained through venous and arterial occlusions, respectively. Known problems with muscle-fiber motion artifacts in optical measurements during exercise were mitigated using a novel gating algorithm that determined muscle contraction status based on control signals from a dynamometer. Results were consistent with previous findings in the literature. This study supports the application of NIRS/DCS technology to quantitatively evaluate hemodynamic and metabolic parameters in exercising skeletal muscle and holds promise for improving diagnosis and treatment evaluation for patients suffering from diseases affecting skeletal muscle and advancing fundamental understanding of muscle and exercise physiology.     

Near-infrared spectroscopy provides an index of blood flow and vasoconstriction in calf skeletal muscle during lower body negative pressure

Aim: Near‐infrared spectroscopy (NIRS) has been used previously for forearm blood flow estimation at rest and during exercise. In this study we applied NIRS to selectively monitor deep calf oxygenated haemoglobin (Hb) responses in order to estimate blood flow changes in the calf muscle during lower body negative pressure (LBNP). The purpose of this study was to test the hypothesis that changes in calf skeletal muscle oxygenated‐Hb, after the removal of superficial tissue responses, were related to blood flow changes during orthostatic stress, and to determine the efficacy of using NIRS measurements as an index of vasoconstriction. Methods: Twenty‐nine subjects participated in this study. All attempted a graded LBNP trial from baseline (0 mmHg) to ?60 mmHg LBNP in 10 mmHg steps at 5‐min intervals. Calf blood flow changes were estimated by oxygenated‐Hb responses in relation to changes in mercury strain gauge plethysmography and muscle sympathetic nerve activity (MSNA). Results: Calf selective deep oxygenated‐Hb decreased continuously from ?10 mmHg LBNP. Regression analysis showed that oxygenated‐Hb was significantly related to declines in plethysmography evaluations of blood flow [oxygenated‐Hb = (?1.57 ± 0.26) + (1.86 ± 0.49) plethysmography, r² = 0.87 ± 0.09]. Changes in MSNA (total activity) were also inversely related to oxygenated‐Hb (slope < 0, P = 0.037; r² = 0.52 ± 0.15). Conclusion: These results suggest that changes in selective deep calf oxygenated‐Hb can be utilized to estimate calf muscle blood flow changes that are most likely caused by vasoconstriction during graded LBNP.     

Anticipatory anxiety-induced changes in human lateral prefrontal cortex activity

It has been suggested that frontal brain asymmetry is associated with differences in basic emotional dimensions, particularly in activation of systems underlying avoidance-withdrawal behavior. We examined regional cerebral oxygenated hemoglobin (O2Hb) levels in human medial prefrontal cortex (MPFC) using near-infrared reflection spectroscopy (NIRS) prior to and during anticipatory anxiety to determine if NIRS could detect any anxiety-related changes. Transient anxiety was induced in 56 normal volunteers by anticipation and a painful shock to the right-hand's median nerve. Pre- and post-anxiety affective statuses were measured using the State-Trait Anxiety Inventory (STAI) and Temperature Character Inventory (TCI). NIRS recorded from the left and right frontal brain regions. Right MPFC O2Hb was significantly increased relative to left MPFC O2Hb during anticipation of the shock. Right-sided O2Hb increases were significantly correlated with the TCI Harm Avoidance subscale. These results support the hypothesis that O2Hb levels in the right frontal region correlate with anxiety or heightened negative affect.     

Assessment of brain oxygenation in term and preterm neonates using near infrared spectroscopy

PurposeThe aim of this study was to determine brain oxygenation in full-term and preterm neonates using near infrared spectroscopy.Material and methodsA total of 88 full-term and preterm newborn infants without hypoxic-ischaemic disorders admitted to the NICU were examined using NIRS on the first day of life and on day 28 of life. Additional measurements were taken at the end of the first week of life in the premature neonates group. Measurements of oxyhaemoglobin (HbO2), deoxyhaemoglobin (Hb), total haemoglobin (HbT) concentration and tissue oxygen saturation (Ox) were performed in 5 brain regions. Right and left frontal areas, the occipital area and right and left temporal areas were measured.ResultsIn full-term healthy neonates a marked decrease in HbO, Hb and HbT values was observed on day 28 of life in all brain regions except the occipital area. In the neonatal period the greatest changes in brain oxygenation occurred in the right and left frontal regions of the brain. In preterm neonates constant values of HbO2 and Ox were observed in the first 28 days of life. In preterm newborn infants, as well as in full term newborn infants, similar Ox and HbO2 values were obtained on day 28 of life.ConclusionsNIRS is a safe method and can be used to evaluate brain oxygenation in newborn infants. The results of these measurements are in accordance with changes in brain oxygenation in the first month of life, which are predicated on the basis of the neonate's physiology.     

Noninvasive determination of brain tissue oxygenation during sleep in obstructive sleep apnea: a near-infrared spectroscopic approach

STUDY OBJECTIVES: Recurrent apneas and hypoxemia during sleep in obstructive sleep apnea (OSA) are associated with profound changes in cerebral blood flow to the extent that cerebral autoregulation may be insufficient to protect the brain. Since the brain is sensitive to hypoxia, the cerebrovascular morbidity seen in OSA could be due to chronic, cumulative effects of intermittent hypoxia. Near-infrared spectroscopy (NIRS) has the potential to noninvasively monitor brain tissue oxygen saturation (SO2), and changes in concentration of oxyhemoglobin [O2Hb], deoxyhemoglobin [HHb] and total hemoglobin [tHb] with real-time resolution. We hypothesized that brain tissue oxygenation would be worse during sleep in OSA relative to controls and sought to determine the practical use of NIRS in the sleep laboratory. DESIGN: We evaluated changes in brain tissue oxygenation using NIRS during overnight polysomnography. SETTING: Studies were conducted at University of Illinois, Chicago and Carle Hospital, Urbana, Illinois. PATIENTS: Nineteen subjects with OSA and 14 healthy controls underwent continuous NIRS monitoring during polysomnography. MEASUREMENTS AND RESULTS: We observed significantly lower indexes of brain tissue oxygenation (SO2: 57.1 +/- 4.9 vs. 61.5 +/- 6.1), [O2Hb]: 22.8 +/- 7.7 vs. 31.5 +/- 9.1, and [tHb]: 38.6 +/- 11.2 vs. 48.6 +/- 11.4 micromol/L) in OSA than controls (all P < 0.05). However, multivariate analysis showed that the differences might be due to age disparity between the two groups. CONCLUSIONS: NIRS is an effective tool to evaluate brain tissue oxygenation in OSA. It provides valuable data in OSA assessment and has the potential to bridge current knowledge gap in OSA.     

Multi-channel near-infrared spectroscopy detects specific inferior-frontal activation during incongruent Stroop trials

Near-infrared spectroscopy (NIRS) is an optical method, which allows non-invasive in vivo measurements of changes in the concentration of oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin in brain tissue. In the present study we investigated 10 healthy subjects by means of multi-channel NIRS (Optical Topography; ETG-100, Hitachi Medical Co., Japan) during performance of congruent and incongruent trials of the Stroop color word task. With a similar pattern of activation for both congruent and incongruent Stroop trials in the NIRS channels located left superior-frontally, the results for O2Hb and the total amount of hemoglobin (Hb-tot) indicate specific activation for interference trials in inferior-frontal areas of the left hemisphere. This result is in line with several neuroimaging studies (fMRI, PET) that have already investigated the frontal activation related to Stroop interference, which further supports the assumption that multi-channel NIRS is sensitive enough to detect spatially specific activation during the performance of cognitive tasks.     

基于近红外光谱的脑立体定向手术导航技术研究

针对目前脑立体定向手术过程中无法解决的穿刺路径偏移问题,提出一种基于近红外光谱技术的神经外科手术实时导航和穿刺路径实时纠错的新方法.通过回归分析建立近红外参数信息和影像信息之间的数学关联模型,通过生物组织光学参数引导手术导航过程;将影像计划穿刺路径锥形化,获得可能偏移路径的灰度信息作为近红外路径偏移纠正的先验知识,采用曲率匹配的算法对偏移路径进行拟合,实现基于近红外光谱技术的术中移位纠错.实验结果表明,提出的方法可以达到近红外实时导航和实时纠偏的目的,并可以实现误差范围内的有效定位,误差范围不超过1 mm.     

Quantification of cerebral hemoglobin as a function of oxygenation using near-infrared time-resolved spectroscopy in a piglet model of hypoxia

Near-infrared spectroscopy (NIRS) has been used for measurement of cerebral hemoglobin (Hb) concentrations in neonates to study cerebral oxygenation and hemodynamics. We perform measurements by portable three-wavelength NIR time-resolved spectroscopy (TRS) in a piglet hypoxia model with various degrees of oxygenation to estimate the absorption coefficient (mu(a)) and reduced scattering coefficient (mu(s)') of the head. Measurements of absolute values of mu(a) at three wavelengths enable estimation of Hb concentration and Hb oxygen saturation in the head (SO2). However, there is a problem concerning which background absorption should be used to estimate Hb concentration in the head derived from mu(a) at three wavelengths because it is different from a simple in vitro model. Therefore, we use two different background absorption values with the assumption that background absorption is due only to 85% (by volume) water or that background absorption is equal to absorption of the piglet head with blood exchange transfusion by fluorocarbon (FC), and we compared SO2 measured by TRS with arterial Hb oxygen saturation (SaO2) and sagittal sinus venous Hb oxygen saturation (SvO2) measured by a co-oximeter at several inspired fractional O2(FI(O2)) concentrations. We find that SO2 values using the absorption (abs) of the piglet head with blood exchange transfusion (BET) by FC are not significantly different from SO2 values using the water-only background at FI(O2) in the range of 15 to 100%, but that the values using abs of the head with BET by FC are lower than the values using the water-only background at FI(O2) in the range of 12 to 4%. The SO2 values calculated from the water-only background are higher than those of SaO2 at FI(O2) in the range of 10 to 4%. However, SO2 values using the abs of the head with BET by FC are between those of SaO2 and SvO2 over the whole range of FI(O2). Therefore, abs of the head with BET by FC is more useful for estimation of the absolute values of oxyHb and deoxyHb of the piglet head.     

Assessment of optical path length in tissue using neodymium and water absorptions for application to near-infrared spectroscopy

Quantitative analysis of blood oxygen saturation using near-IR spectroscopy is made difficult by uncertainties in both the absolute value and the wavelength dependence of the optical path length. We introduce a novel means of assessing the wavelength dependence of path length, exploiting the relative intensities of several absorptions exhibited by an exogenous contrast agent (neodymium). Combined with a previously described method that exploits endogenous water absorptions, the described technique estimates the absolute path length at several wavelengths throughout the visible/near-IR range of interest. Isolated rat hearts (n = 11) are perfused separately with Krebs-Henseleit buffer (KHB) and a KHB solution to which neodymium had been added, and visible/near-IR spectra are acquired using an optical probe made up of emission and collection fibers in concentric rings of diameters 1 and 3 mm, respectively. Relative optical path lengths at 520, 580, 679, 740, 800, 870, and 975 nm are 0.41+/-0.13, 0.49+/-0.21, 0.90+/-0.09, 0.94+/-0.01, 1.00, 0.84+/-0.01, and 0.78+/-0.08, respectively. The absolute path length at 975 nm is estimated to be 3.8+/-0.6 mm, based on the intensity of the water absorptions and the known tissue water concentration. These results are strictly valid only for the experimental geometry applied here.     

Investigation of human brain hemodynamics by simultaneous near-infrared spectroscopy and functional magnetic resonance imaging

The aim of this study was to compare functional cerebral hemodynamic signals obtained simultaneously by near infrared spectroscopy (NIRS) and by functional magnetic resonance imaging (fMRI). The contribution of superficial layers (skin and skull) to the NIRS signal was also assessed. Both methods were used to generate functional maps of the motor cortex area during a periodic sequence of stimulation by finger motion and rest. In all subjects we found a good collocation of the brain activity centers revealed by both methods. We also found a high temporal correlation between the BOLD signal (fMRI) and the deoxy-hemoglobin concentration (NIRS) in the subjects who exhibited low fluctuations in superficial head tissues.     

A novel noninvasive all optical technique to monitor physiology of an exercising muscle

An all optical technique based on near-infrared spectroscopy and mid-infrared imaging (MIRI) is applied as a noninvasive, in vivo tool to monitor the vascular status of skeletal muscle and the physiological changes that occur during exercise. A near-infrared spectroscopy (NIRS) technique, namely, steady state diffuse optical spectroscopy (SSDOS) along with MIRI is applied for monitoring the changes in the values of tissue oxygenation and thermometry of an exercising muscle. The NIRS measurements are performed at five discrete wavelengths in a spectral window of 650-850 nm and MIRI is performed in a spectral window of 8-12 microm. The understanding of tissue oxygenation status and the behavior of the physiological parameters derived from thermometry may provide a useful insight into muscle physiology, therapeutic response and treatment.     

Cerebral oxygenation changes in the prefrontal cortex: effects of age and gender

Multi-channel near-infrared spectroscopy (NIRS) is an optical method, which allows non-invasive in vivo measurements of changes in the concentration of oxygenated (O(2)Hb) and deoxygenated (HHb) hemoglobin in living brain tissue, simultaneously from multiple measurement points. In the present study, 44 young and 42 elderly subjects were investigated by means of multi-channel NIRS (optical topography) during performance of the verbal fluency task (VFT). The aim of the study was to analyze the effects of the subjects' age and gender on functional brain activation during this cognitive task. In summary, the results clearly show that the VFT activated the left and right dorsolateral prefrontal cortex (increases in O(2)Hb and more localized decreases in HHb), with an obvious left-hemispheric dominance. The elderly subjects generally exhibited less activation and no left hemispheric lateralization effect. In contrast to a previous study, we did not find a clear influence of the subjects' gender on the brain activation pattern.