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Frequency domain near infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS) have emerged as synergistic techniques for the non-invasive assessment of tissue health. Combining FD-NIRS oximetry with DCS measures of blood flow, the tissue oxygen metabolic rate can be quantified, a parameter more closely linked to underlying physiology and pathology than either NIRS or DCS estimates alone. Here we describe the first commercially available integrated instrument, called the “MetaOx”, designed to enable simultaneous FD-NIRS and DCS measurements at rates of 10 + Hz, and offering real-time data evaluation. We show simultaneously acquired characterization data demonstrating performance equivalent to individual devices and sample in vivo measurements of pulsation resolved blood flow, forearm occlusion hemodynamic changes and muscle oxygen metabolic rate monitoring during stationary bike exercise.

Cerebral blood flow (CBF) during stepped hypercapnia was measured simultaneously in the rat brain using near-infrared diffuse correlation spectroscopy (DCS) and arterial spin labeling MRI (ASL). DCS and ASL CBF values agree very well, with high correlation (R=0.86, p< 10-9), even when physiological instability perturbed the vascular response. A partial volume effect was evident in the smaller magnitude of the optical CBF response compared to the MRI values (averaged over the cortical area), primarily due to the inclusion of white matter in the optically sampled volume. The 8.2 and 11.7 mm mid-separation channels of the multi-distance optical probe had the lowest partial volume impact, reflecting ~75 % of the MR signal change. Using a multiplicative correction factor, the ASL CBF could be predicted with no more than 10% relative error, affording an opportunity for real-time relative cerebral metabolism monitoring in conjunction with MR measurement of cerebral blood volume using super paramagnetic contrast agents.

Near-infrared spectroscopy (NIRS) is a noninvasive neuroimaging tool for studying evoked hemodynamic changes within the brain. By this technique, changes in the optical absorption of light are recorded over time and are used to estimate the functionally evoked changes in cerebral oxyhemoglobin and deoxyhemoglobin concentrations that result from local cerebral vascular and oxygen metabolic effects during brain activity. Over the past three decades this technology has continued to grow, and today NIRS studies have found many niche applications in the fields of psychology, physiology, and cerebral pathology. The growing popularity of this technique is in part associated with a lower cost and increased portability of NIRS equipment when compared with other imaging modalities, such as functional magnetic resonance imaging and positron emission tomography. With this increasing number of applications, new techniques for the processing, analysis, and interpretation of NIRS data are continually being developed. We review some of the time-series and functional analysis techniques that are currently used in NIRS studies, we describe the practical implementation of various signal processing techniques for removing physiological, instrumental, and motion-artifact noise from optical data, and we discuss the unique aspects of NIRS analysis in comparison with other brain imaging modalities. These methods are described within the context of the MATLAB-based graphical user interface program, HomER, which we have developed and distributed to facilitate the processing of optical functional brain data.

Although most current diffuse optical brain imaging systems use only nearest- neighbor measurement geometry, the spatial resolution and quantitative accuracy of the imaging can be improved through the collection of overlapping sets of measurements. A continuous-wave diffuse optical imaging system that combines frequency encoding with time-division multiplexing to facilitate overlapping measurements of brain activation is described. Phantom measurements to confirm the expected improvement in spatial resolution and quantitative accuracy are presented. Experimental results showing the application of this instrument for imaging human brain activation are also presented. The observed improvement in spatial resolution is confirmed by functional magnetic resonance imaging.

We compare two geometries of sources and detectors for optimizing the diffuse optical imaging resolution of brain activation in humans. Because of limitations in the instruments' dynamic range, most diffuse optical brain activation images have used only nonoverlapping measurements. We demonstrate theoretically and with a human experiment that a simple geometry of sources and detectors can provide overlapping measurements within the limitation of instrumentation dynamic range and produce an image resolution and localization accuracy that is twofold better.

We describe a method to characterize spatial or temporal changes in the optical properties of turbid media using diffuse reflectance images acquired under broad-beam illumination conditions. We performed experiments on liquid phantoms whose absorption (mu(a)) and reduced scattering (mu(s)') coefficients were representative of those of biological tissues in the near infrared. We found that the relative diffuse reflectance R depends on mu(a) and mu(s)' only through the ratio mu(a)/mu(s)' and that dependence can be well described with an analytical expression previously reported in the literature [S. L. Jacques, Kluwer Academic Dordrecht (1996)]. We have found that this expression for R deviates from experimental values by no more than 8% for various illumination and detection angles within the range 0 degrees-30 degrees. Therefore, this analytical expression for R holds with good approximation even if the investigated medium presents curved or irregular surfaces. Using this expression, it is possible to translate spatial or temporal changes in the relative diffuse reflectance from a turbid medium into quantitative estimates of the corresponding changes of (mu(a)/mu(s)')(1/2). In the case of media with optical properties similar to those of tissue in the near infrared, we found that the changes mu(a)/mu(s)' should occur over a volume approximately 2 mm deep and 4 mm x 4 mm wide to apply this expression.

We have developed an instrument for non-invasive optical imaging of the human brain that produces on-line images with a temporal resolution of 160 ms. The imaged quantities are the temporal changes in cerebral oxy-hemoglobin and deoxy-hemoglobin concentrations. We report real-time videos of the arterial pulsation and motor activation recorded on a 4×9 cm2area of the cerebral cortex in a healthy human subject. This approach to optical brain imaging is a powerful tool for the investigation of the spatial and temporal features of the optical signals collected on the brain. © 2000 Optical Society of America.

We have experimentally investigated the meaning of the effective optical absorption @ma ~eff ! # and the reduced scattering @ms9 ~eff ! # coefficients measured on the surfaces of two-layered turbid media, using the diffusion equation for homogeneous, semi-infinite media. We performed frequency-domain spectroscopy in a reflectance geometry, using source‐detector distances in the range 1.5‐ 4.5 cm. We measured 100 samples, each made of one layer ~thickness in the range 0.08 ‐1.6 cm! on top of one semi-infinite block. The optical properties of the samples were similar to those of soft tissues in the near infrared. We found that the measured effective optical coefficients are representative of the underlying block if the superficial layer is less than ;0.4 cm thick, whereas they are representative of the superficial layer if it is more than ;1.3 cm thick. © 1998 Optical Society of America OCIS codes: 170.5280, 170.6510, 170.7050, 300.0300, 300.6340.

The Green's function for the diffusion equation is widely used to describe photon transport in turbid media. We have performed a series of spectroscopy experiments on a number of uniform turbid media with different optical properties (absorption coefficient in the range 0.03-0.14 cm-1, reduced scattering coefficient in the range 5-22 cm-1). Our experiments have been conducted in the frequency domain, where the measured parameters are the dc intensity (Idc), ac amplitude (Iac), and phase (Φ) of the light intensity wave. In an infinite medium, the Green's function predicts a linear dependence of ln(rIdc) and Φ on the source-detector separation r. Our measurements show that the intercepts of these straight lines predicted by the Green's function do not agree with the experimental results. To reproduce the experimental results, we have introduced an effective photon source whose spatial extent and source strength depend on the optical properties of the medium. This effective source term has no effect on the slopes of the straight lines predicted by the Green's function at large values of r. © 1997 Optical Society of America.

We have measured the optical absorption and scattering coefficient spectra of a multiple-scattering medium (i.e., a biological tissue-simulating phantom comprising a lipid colloid) containing methemoglobin by using frequency-domain techniques. The methemoglobin absorption spectrum determined in the multiple-scattering medium is in excellent agreement with a corrected methemoglobin absorption spectrum obtained from a steady-state spectrophotometer measurement of the optical density of a minimally scattering medium. The determination of the corrected methemoglobin absorption spectrum takes into account the scattering from impurities in the methemoglobin solution containing no lipid colloid. Frequency-domain techniques allow for the separation of the absorbing from the scattering properties of multiple-scattering media, and these techniques thus provide an absolute measurement of the optical absorption spectra of the methemoglobin/lipid colloid suspension. One accurately determines the absolute methemoglob in absorption spectrum in the frequency domain by extracting the scattering and absorption coefficients from the phase shift Φ and average light intensity DC (or Φ and the amplitude of the light-intensity oscillations AC) data with relationships provided by diffusion theory, but one determines it less accurately by using the Φ and modulation M (M ≡ AC/DC) data and the diffusion theory relationships. In addition to the greater uncertainty in the absorption and scattering coefficients extracted from the Φ and M data, the optical parameters extracted from the Φ and M data exhibit systematically inaccurate behavior that cannot be explained by random noise in the system. Possible reasons for the systematically lower accuracy of the methemoglobin absorption spectrum obtained from Φ and M data are discussed.

Tissue glucose levels affect the refractive index of the extracellular fluid. The difference in refractive index between the extracellular fluid and the cellular components plays a role in determining the reduced scattering coefficient (micro(s)') of tissue. Hence a physical correlation may exist between the reduced scattering coefficient and glucose concentration. We have designed and constructed a frequency-domain near-infrared tissue spectrometer capable of measuring the reduced scattering coefficient of tissue with enough precision to detect changes in glucose levels in the physiological and pathological range.

We have studied light migration in highly scattering media theoretically and experimentally, using the We approximation in a semi-infinite-geometry boundary condition. Both the light source and the diffusion detector were located on the surface of a semi-infinite medium. Working with frequency-domain spectroscopy, we approached the problem in three areas: (1) we derived theoretical expressions for the measured quantities spectroscopy by applying appropriate boundary conditions to the diffusion equation; (2) in frequency-domain we experimentally verified the theoretical expressions by performing measurements on a macroscopically medium in quasi-semi-infinite-geometry conditions; (3) we applied Monte Carlo methods to homogeneous the semi-infinite-geometry boundary problem. The experimental results and the confirming Monte simulate Carlo simulation show that the diffusion approximation, under the appropriate boundary conditions, accurately estimates the optical parameters of the medium.