In vivo determination of the optical properties of infant brain using frequency-domain near-infrared spectroscopy

We investigate the optical properties of the brain in 23 neonates in vivo using a frequency domain near-infrared spectroscopy (NIRS). In this study, a calibration procedure is employed to determine the absorption and reduced scattering coefficients with single source-detector separation. The absorption coefficients of the infant foreheads are lower than the values reported in adults. A large intersubject variation in the reduced scattering coefficients is also demonstrated. Furthermore, physiological parameters are derived from the absorption coefficients at two wavelengths (788 and 832 nm). The mean total hemoglobin concentration (THC) is 39.7+/-9.8 microM and the mean cerebral blood oxygen saturation (StO2) is 58.7+/-11.2%. Our preliminary results show that this bedside frequent domain NIRS could provide quantitative optical measurement of the infant brain.     

In vivo determination of skin near-infrared optical properties using diffuse optical spectroscopy

We develop a superficial diffusing probe with a 3 mm source-detector separation that can be used in combination with diffuse optical spectroscopic (DOS) methods to noninvasively determine full-spectrum optical properties of superficial in vivo skin in the wavelength range from 650 to 1000 nm. This new probe uses a highly scattering layer to diffuse photons emitted from a collimated light source and relies on a two-layer diffusion model to determine tissue absorption coefficient mu a and reduced scattering coefficient mu's. By employing the probe to measure two-layer phantoms that mimic the optical properties of skin, we demonstrate that the probe has an interrogation depth of 1 to 2 mm. We carry out SSFDPM (steady state frequency-domain photon migration) measurements using this new probe on the volar forearm and palm of 15 subjects, including five subjects of African descent, five Asians, and five Caucasians. The optical properties of in vivo skin determined using the superficial diffusing probe show considerable similarity to published optical properties of carefully prepared ex vivo epidermis+dermis.     

Noninvasive detection of functional brain activity with near-infrared diffusing-wave spectroscopy

We use near-infrared dynamic multiple scattering of light [diffusing-wave spectroscopy (DWS)] to detect the activation of the somato-motor cortex in 11 right-handed volunteers performing a finger opposition task separately with their right and left hands. Temporal autocorrelation functions g(1)(r,tau) of the scattered light field are measured during 100-s periods of motor task alternating with 100-s resting baseline periods. From an analysis of the experimental data with an analytical theory for g(1)(r,tau) from a three-layer geometry with optical and dynamical heterogeneity representing scalp, skull, and cortex, we obtain quantitative estimates of the diffusion coefficient in cortical regions. Consistent with earlier results, the measured cortical diffusion coefficient is found to be increased during the motor task, with a strong contralateral and a weaker ipsilateral increase consistent with the known brain hemispheric asymmetry for right-handed subjects. Our results support the interpretation of the increase of the cortical diffusion coefficient during finger opposition being due to the functional increase in cortical blood flow rate related to vasodilation.     

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.     

Effect of errors in baseline optical properties on accuracy of transabdominal near-infrared spectroscopy in fetal sheep brain during hypoxic stress

A continuous-wave (cw) near-infrared spectroscopy (NIRS) instrument has been developed to noninvasively quantify fetal cerebral blood oxygen saturation (StO2). A linear Green's function formulism was used to analytically solve the photon diffusion equation and extract the time-varying fetal tissue oxy- and deoxy-hemoglobin concentrations from the NIR measurements. Here we explored the accuracy with which this instrument can be expected to perform over a range of fetal hypoxic states. We investigated the dependence of this accuracy on the accuracy of the reference optical properties chosen based on the literature. The fetal oxygenation of a pregnant ewe model was altered via maternal aortic occlusion. The NIR cw instrument was placed on the maternal abdomen directly above the fetal head, continuously acquiring diffuse optical measurements. Blood was sampled periodically from the fetus to obtain fetal arterial saturation (SaO2) measurements from blood gas analysis. The NIR StO2 values were compared with the fetal SaO2 measurements. Variations in the NIR results due to uncertainty in the reference optical properties were relatively small within the fetal SaO2 range of 30 to 80%. Under hypoxic conditions, however, the variability of the NIR StO2 calculations with changes in the assumed reference properties became more significant.     

Reevaluation of near-infrared light propagation in the adult human head: implications for functional near-infrared spectroscopy

Using both experimental and theoretical methods, we examine the contribution of different parts of the head to near-IR (NIR) signal. Time-resolved spectroscopy is employed to measure the mean optical path length (PL), and the absorption (mu(a)) and reduced scattering (mu(s)') coefficients in multiple positions of the human head. Monte Carlo simulations are performed on four-layered head models based on an individual magnetic resonance imaging (MRI) scan to determine mu(a) and mu(s)' in each layer of the head by solving inverse problems, and to estimate the partial path length in the brain (p-PL) and the spatial sensitivity to regions in the brain at the source-detector separation of 30 mm. The PL is closely related to the thickness of the scalp, but not to that of other layers of the head. The p-PL is negatively related to the PL and its contribution ratio to the PL is 5 to 22% when the differential path length factor is 6. Most of the signal attributed to the brain comes from the upper 1 to 2 mm of the cortical surface. These results indicate that the NIR signal is very sensitive to hemodynamic changes associated with functional brain activation in the case that changes in the extracerebral tissue are ignorable.     

Noninvasive monitoring of hemodynamic stress using quantitative near-infrared frequency-domain photon migration spectroscopy

Hemorrhagic hypovolemia and inotropic agent administration were used to manipulate cardiac output (CO) and oxygen delivery in rabbits to investigate the correlation between noninvasive frequency domain photon migration (FDPM) spectroscopy and invasive hemodynamic monitoring parameters. Frequency-domain photon migration provides quantitative measurements of light absorption and reduced scattering (mu(a) and mu(s)(prime prime or minute), respectively) in tissue. Wavelength dependent mu(a) values were used to calculate in vivo tissue concentration of deoxyhemoglobin [Hb], oxyhemoglobin [HbO(2)], total hemoglobin [TotHb], and water [H(2)O] as well as mixed arterial-venous oxygen saturation (S(t)O(2)) in tissue. FDPM-derived physiologic properties were correlated with invasive measurements of CO and mean pulmonary artery pressure (mPAP), FDPM-derived [TotHb] and S(t) O(2) correlated significantly with hemorrhaged volume (HV), mPAP, and CO. Correlation coefficients for [TotHb] vs HV, mPAP, and CO were -0.77, 0.86, and 0.70, respectively. Correlation coefficients of S(t)O( 2) vs HV, mPAP, and CO were -0.71, 0.55, and 0.61, respectively. Dobutamine induced changes resulted in correlation coefficients between FDPM-derived and invasively measured physiologic parameters that are comparable to those induced by hypovolemia. FDPM spectroscopy is sensitive to changes in mPAP and CO of as little as 15%. These results suggest that FDPM spectroscopy may be used in clinical settings to noninvasively monitor central hemodynamic parameters and to directly assess oxygenation of tissues.     

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.     

Noninvasive observation of skeletal muscle contraction using near-infrared time-resolved reflectance and diffusing-wave spectroscopy

We introduce a method for noninvasively measuring muscle contraction in vivo, based on near-infrared diffusing-wave spectroscopy (DWS). The method exploits the information about time-dependent shear motions within the contracting muscle that are contained in the temporal autocorrelation function g(1)(τ,t) of the multiply scattered light field measured as a function of lag time, τ, and time after stimulus, t. The analysis of g(1)(τ,t) measured on the human M. biceps brachii during repetitive electrical stimulation, using optical properties measured with time-resolved reflectance spectroscopy, shows that the tissue dynamics giving rise to the speckle fluctuations can be described by a combination of diffusion and shearing. The evolution of the tissue Cauchy strain e(t) shows a strong correlation with the force, indicating that a significant part of the shear observed with DWS is due to muscle contraction. The evolution of the DWS decay time shows quantitative differences between the M. biceps brachii and the M. gastrocnemius, suggesting that DWS allows to discriminate contraction of fast- and slow-twitch muscle fibers.     

Performance of a lookup table-based approach for measuring tissue optical properties with diffuse optical spectroscopy

Diffuse optical spectroscopy (DOS) provides a powerful tool for fast and noninvasive disease diagnosis. The ability to leverage DOS to accurately quantify tissue optical parameters hinges on the model used to estimate light-tissue interaction. We describe the accuracy of a lookup table (LUT)-based inverse model for measuring optical properties under different conditions relevant to biological tissue. The LUT is a matrix of reflectance values acquired experimentally from calibration standards of varying scattering and absorption properties. Because it is based on experimental values, the LUT inherently accounts for system response and probe geometry. We tested our approach in tissue phantoms containing multiple absorbers, different sizes of scatterers, and varying oxygen saturation of hemoglobin. The LUT-based model was able to extract scattering and absorption properties under most conditions with errors of less than 5 percent. We demonstrate the validity of the lookup table over a range of source-detector separations from 0.25 to 1.48 mm. Finally, we describe the rapid fabrication of a lookup table using only six calibration standards. This optimized LUT was able to extract scattering and absorption properties with average RMS errors of 2.5 and 4 percent, respectively.     

Accuracy limits in the determination of absolute optical properties using time-resolved NIR spectroscopy.

We assess typical systematic experimental errors involved in a time-resolved measurement as applied to NIR diffuse optical spectroscopy and investigate their effect on the quantification accuracy of the absorption and the reduced scattering coefficient. We demonstrate that common systematic experimental uncertainties may lead to quantification errors of 10% or more, even when excellent signal to noise ratio conditions exist and accurate photon propagation models are employed. We further demonstrate that the accuracy of the calculation depends nonlinearly on the optical properties of the medium measured. High scattering and low absorbing media can be quantified more accurately than media with low scattering or high absorption using measurements of the same signal to noise ratio. We further discuss curve-shape fitting schemes that aid in improving the quantification accuracy in the presence of experimental errors. Finally, we identify uncertainties that set quantification accuracy limits and we find temporal resolution as the ultimate limiting factor in the quantification accuracy achieved. Our findings suggest that temporal resolution of the order of 10 ps is necessary for quantifying the absorption and reduced scattering coefficient of diffuse media with accuracy better than 5% using curve fitting methods. In that sense this analysis can be used in time-resolved system design and in predicting the expected errors given the technology selected for time-resolved measurements.     

Efficient determination of the epidermal optical properties using a diffusion model-based approach: Monte Carlo studies

In our previous studies, we have shown that the diffusing probe geometry can be used in conjunction with a two-layer diffusion model to accurately recover the absorption and scattering properties of skin in vivo. By modifying the original design to the diffusing probe with planar source (DPPS) geometry, we have also demonstrated that the efficiency of the accompanying multilayer diffusion model is comparable to that of a standard semi-infinite diffusion model; thus, precise quantification of superficial tissue optical properties in real time using a diffusion model becomes possible. In this study, the performance of the DPPS diffusion model is evaluated using Monte Carlo simulations and phantom measurements. It is found that the DPPS geometry is advantageous over the conventional planar source illumination geometry in interrogating superficial volumes of samples. In addition, our simulation results have shown that the DPPS geometry is capable of accurately recovering the optical properties of 50-μm thick epidermis and could be very useful in detecting cutaneous melanoma that has a radius as small as 250 μm.     

Analysis of near-infrared spectroscopy and indocyanine green dye dilution with Monte Carlo simulation of light propagation in the adult brain

Near-infrared spectroscopy (NIRS) combined with indocyanine green (ICG) dilution is applied externally on the head to determine the cerebral hemodynamics of neurointensive care patients. We applied Monte Carlo simulation for the analysis of a number of problems associated with this method. First, the contamination of the optical density (OD) signal due to the extracerebral tissue was assessed. Second, the measured OD signal depends essentially on the relative blood content (with respect to its absorption) in the various transilluminated tissues. To take this into account, we weighted the calculated densities of the photon distribution under baseline conditions within the different tissues with the changes and aberration of the relative blood volumes that are typically observed under healthy and pathologic conditions. Third, in case of NIRS ICG dye dilution, an ICG bolus replaces part of the blood such that a transient change of absorption in the brain tissues occurs that can be recorded in the OD signal. Our results indicate that for an exchange fraction of Delta=30% of the relative blood volume within the intracerebral tissue, the OD signal is determined from 64 to 74% by the gray matter and between 8 to 16% by the white matter maximally for a distance of d=4.5 cm.     

Functional near-infrared optical imaging: utility and limitations in human brain mapping

Although near-infrared spectroscopy (NIRS) was developed as a tool for clinical monitoring of tissue oxygenation, it also has potential for neuroimaging. A wide range of different NIRS instruments have been developed, and instruments for continuous intensity measurements with fixed spacing [continuous wave (CW)-type instruments], which are most readily available commercially, allow us to see dynamic changes in regional cerebral blood flow in real time. However, quantification, which is necessary for imaging of brain functions, is impossible with these CW-type instruments. Over the past 20 years, many different approaches to quantification have been tried, and several multichannel time-resolved and frequency-domain instruments are now in common use for imaging. Although there are still many problems with this technique, such as incomplete knowledge of how light propagates through the head, NIRS will not only open a window on brain physiology for subjects who have rarely been examined until now, but also provide a new direction for functional mapping studies.     

Noninvasive assessment of breast cancer risk using time-resolved diffuse optical spectroscopy

Breast density is a recognized strong and independent risk factor for breast cancer. We propose the use of time-resolved transmittance spectroscopy to estimate breast tissue density and potentially provide even more direct information on breast cancer risk. Time-resolved optical mammography at seven wavelengths (635 to 1060 nm) is performed on 49 subjects. Average information on breast tissue of each subject is obtained on oxy- and deoxyhemoglobin, water, lipids, and collagen content, as well as scattering amplitude and power. All parameters, except for blood volume and oxygenation, correlate with mammographic breast density, even if not to the same extent. A synthetic optical index proves to be quite effective in separating different breast density categories. Finally, the estimate of collagen content as a more direct means for the assessment of breast cancer risk is discussed.     

In vivo optical characterization of human prostate tissue using near-infrared time-resolved spectroscopy

The development of photodynamic therapy into a modality for treatment of prostate cancer calls for reliable optical dosimetry. We employ, for the first time, interstitial time-resolved spectroscopy to determine in vivo optical properties of human prostate tissue. Nine patients are included in the study, and measurements are conducted prior to primary brachytherapy treatment of prostate cancer. Intrasubject variability is examined by measuring across three tissue volumes within each prostate. The time-resolved instrumentation proves its usefulness by producing good signal levels in all measurements. We are able to present consistent values on reduced scattering coefficients (mu(s)'), absorption coefficients (mu(a)), and effective attenuation (mu(eff)) at the wavelengths 660, 786, and 916 nm. At 660 nm, mu(s)' is found to be 9+/-2 cm(-1), and mu(a) is 0.5+/-0.1 cm(-1). Derived values of mu(eff) are in the range of 3 to 4 cm(-1) at 660 nm, a result in good agreement with previously published steady state data. Total hemoglobin concentration (THC) and oxygen saturation are spectroscopically determined using derived absorption coefficients. Derived THC values are fairly variable (215+/-65 microM), while derived values of oxygen saturation are gathered around 75% (76+/-4%). Intrasubject variations in derived parameters correlate (qualitatively) with the heterogeneity exhibited in acquired ultrasound images.     

Progress of near-infrared spectroscopy and topography for brain and muscle clinical applications

This review celebrates the 30th anniversary of the first in vivo near-infrared (NIR) spectroscopy (NIRS) publication, which was authored by Professor Frans Jobsis. At first, NIRS was utilized to experimentally and clinically investigate cerebral oxygenation. Later it was applied to study muscle oxidative metabolism. Since 1993, the discovery that the functional activation of the human cerebral cortex can be explored by NIRS has added a new dimension to the research. To obtain simultaneous multiple and localized information, a further major step forward was achieved by introducing NIR imaging (NIRI) and tomography. This review reports on the progress of the NIRS and NIRI instrumentation for brain and muscle clinical applications 30 years after the discovery of in vivo NIRS. The review summarizes the measurable parameters in relation to the different techniques, the main characteristics of the prototypes under development, and the present commercially available NIRS and NIRI instrumentation. Moreover, it discusses strengths and limitations and gives an outlook into the "bright" future.     

Questioning the questions that have been asked about the infant brain using near-infrared spectroscopy

Near-infrared spectroscopy (NIRS) is a noninvasive diffuse optical-imaging technique that can measure local metabolic demand in the surface of the cortex due to differential absorption of light by oxygenated and deoxygenated blood. Over the past decade, NIRS has become increasingly used as a complement to other neuroimaging techniques, such as electroencephalography (EEG), magnetoencephalography (MEG), and functional magnetic resonance imaging (fMRI), particularly in paediatric populations who cannot easily be tested using fMRI and MEG. In this review of empirical findings from human infants, ranging in age from birth to 12 months of age, a number of interpretive concerns are raised about what can be concluded from NIRS data. In addition, inconsistencies across studies are highlighted, and strategies are proposed for enhancing the reliability of NIRS data gathered from infants. Finally, a variety of new and promising advances in NIRS techniques are highlighted.     

Shades of gray matter: Noninvasive optical images of human brain reponses during visual stimulation

Recent theories about human brain function emphasize the need for imaging methods that allow the study of dynamic interactions among different structures. In this paper, we report on a new technique, based on the measurement of parameters of migration of near-infrared photons, that yields functional images of the human occipital cortex, combining a spatial resolution of 0.5 cm and a temporal resolution of 50 ms. This technique appears to be suitable for studying the dynamics of cortical activation.