Objective assessment of olfactory function has diagnostic and legal value. We have designed an odor detection task in which the subject reported the conscious sensing of an odorant via a button press while the hemodynamic activity from the forehead was monitored using a 4-channel fNIRS system. The task consisted of intermingled odor and non-odor trials. We recorded from 17 subjects and each of them underwent 60 trials. The time domain analysis of the raw data showed that the hemodynamic activity was statistically different between the odor and non-odor trials especially for oxyhemoglobin in far channels. In order to single out the odor-induced hemodynamic response from that of motor activity, finger tapping was considered as a control condition for odor detection. Pairwise correlation indicated that motor activity had a short lasting influence on hemodynamic response while the hemodynamic response to different odors were highly correlated over time. In conclusion, we believe that fNIRS monitoring of hemodynamic response could be potentially used for objective assessment of odor detection in cases that subjective report is unreliable.
Functional near-infrared spectroscopy (fNIRS) has recently been suggested for monitoring cortical hemodynamic response to experimental and clinical acute pain. However, the hemodynamic response to a tonic, noxious cold stimulus, and its relation with subjective pain sensation is not fully characterized. We investigated the relationship between pain threshold and tolerance and the evoked hemodynamic response to cold pressor tests (CPTs) at varying intensities and explored the gender effect. Twenty-one healthy individuals (10 males and 11 females) performed four CPTs at 1°C, 5°C, 10°C, and 15°C. Deoxyhemoglobin (HHb) and oxyhemoglobin (HbO2) were measured continuously on the forehead by two “far” and two “near” channels in addition to pain scores, threshold, and tolerance. We found a significant within-subject correlation between pain threshold and the immediate HbO2 response at the right frontal region. Gender difference and asymmetrical activation were observed in the “far” channels but not the “near” channels, suggesting a hemispheric preference in response to noxious cold stimuli. No gender difference was found in pain threshold, tolerance, or scores. This research adds to the body of literature suggesting the use of fNIRS for bedside assessment of pain in addition to behavioral and subjective measures for comprehensive, multimodal pain management.
We introduce the application of functional data analysis (fDA) on functional near-infrared spectroscopy (fNIRS) signals for the development of an accurate and clinically practical assessment method of pain perception. We used the cold pressor test to induce different levels of pain in healthy subjects while the fNIRS signal was recorded from the frontal regions of the brain. We applied fDA on the collected fNIRS data to convert discrete samples into continuous curves. This method enabled us to represent the curves as a linear combination of basis functions. We utilized bases coefficients as features that represent the shape of the signals (as opposed to extracting defined features from signal) and used them to train a support vector machine to classify the signals based on the level of induced pain. We achieved 94% of accuracy to classify low-pain and high-pain signals. Moreover applying hierarchical clustering on the coefficients, we found three clusters in the data which represented low-pain (one cluster) and high-pain groups (two clusters) with an accuracy of 91.2%. The center of these clusters can represent the prototype fNIRS response of that pain level.
A system integrating high density diffuse optical imaging with adaptive optics using MEMS for deep tissue interaction is presented. In this system, a laser source is scanned over a high density fiber bundle using Digital Micromirror Device (DMD) and channeled to a tissue phantom. Backscatter is then collected from the tissue phantom by a high density fiber array of different fiber type and channeled to CMOS sensor for image acquisition. Intensity focus is directly verified using a second CMOS sensor which measures intensity transmitted though the tissue phantom. A set of training patterns are displayed on the DMD and backscatter is numerically fit to the transmission intensity. After the training patterns are displayed, adaptive focus is performed using only the backscatter and fitting functions. Additionally, tissue reconstruction and prediction of interference focusing by photoacoustic and optical tomographic methods is discussed. Finally, potential NIR applications such as in-vivo adaptive neural photostimulation and cancer targeting are discussed.
KEYWORDS: Hemodynamics, Data analysis, Functional near infrared spectroscopy, Principal component analysis, Smoothing, Tissues, Canonical correlation analysis, Data conversion, Near infrared, Functional magnetic resonance imaging
Functional near infrared spectroscopy (fNIRS) is a powerful tool for the study of oxygenation and hemodynamics of living tissues. Despite the continuous nature of the processes generating the data, analysis of fNIRS data has been limited to discrete-time methods. We propose a technique, namely functional data analysis (fDA), that converts discrete samples to continuous curves. We used fNIRS data collected on forehead during a cold pressor test (CPT) from 20 healthy subjects. Using functional principal component analysis, oxyhemoglobin (HbO 2 ) and deoxyhemoglobin (Hb) curves were decomposed into several components based on variability across the subjects. Each component corresponded to an experimental condition and provided qualitative and quantitative information of the shape and weight of that component. Furthermore, we applied functional canonical correlation analysis to investigate the interaction between Hb and HbO 2 curves. We showed that the variation of Hb and HbO 2 was positively correlated during the CPT, with a “far” channel on right forehead showing a smaller and faster HbO 2 variation than Hb. This research suggests the fDA platform for the analysis of fNIRS data, which solves problem of high dimensionality, enables study of response dynamics, enhances characterization of the evoked response, and may improve design of future fNIRS experiments.
Modeling behavior of broadband (30 to 1000 MHz) frequency modulated near-infrared (NIR) photons through a phantom is the basis for accurate extraction of optical absorption and scattering parameters of biological turbid media. Photon dynamics in a phantom are predicted using both analytical and numerical simulation and are related to the measured insertion loss (IL) and insertion phase (IP) for a given geometry based on phantom optical parameters. Accuracy of the extracted optical parameters using finite element method (FEM) simulation is compared to baseline analytical calculations from the diffusion equation (DE) for homogenous brain phantoms. NIR spectroscopy is performed using custom-designed, broadband, free-space optical transmitter (Tx) and receiver (Rx) modules that are developed for photon migration at wavelengths of 680, 780, and 820 nm. Differential detection between two optical Rx locations separated by 0.3 cm is employed to eliminate systemic artifacts associated with interfaces of the optical Tx and Rx with the phantoms. Optical parameter extraction is achieved for four solid phantom samples using the least-square-error method in MATLAB (for DE) and COMSOL (for FEM) simulation by fitting data to measured results over broadband and narrowband frequency modulation. Confidence in numerical modeling of the photonic behavior using FEM has been established here by comparing the transmission mode’s experimental results with the predictions made by DE and FEM for known commercial solid brain phantoms.
Metallic nanoparticle inks - colloidal suspensions of silver or gold nanoparticles in water or other organic solvents - can
be sintered at relatively low temperatures (70 - 200°C). With appropriate thermal treatment the sintering can be
controlled to fabricate nanoparticle substrates with a distribution of clusters sizes and interparticle distances. Such
substrates exhibit relatively high (108 - 109) surface enhanced Raman scattering (SERS) amplification factors (AFs). The high AFs in such substrates arise from several mechanisms. The 'dimers' - two nanoparticles separated by a nanometersize
gap - are known to produce amplification of the local electric field orders of magnitude larger than at the surface of
an isolated single nanoparticle due to surface plasmon resonance. Furthermore, the lack of translational symmetry in the
clusters leads to localizations of electromagnetic excitations to very small regions that can create SERS hot spots. Here
we report that microwave absorption (~ 10 GHz) as a function of thermal annealing in dry-drop substrates can be used to
monitor the sintering process in metallic nanoparticle inks. The predominant contribution to microwave absorption comes from electrically resistive weak links that are formed between nanoparticles as a result of the thermal treatment. Just before the creation of these weak links, such nanoparticle pairs are also the ones that make a major contribution to the SERS AFs. This leads to a correlation between the observed microwave absorption and the SERS signal intensities. We also present a simple model that describes the microwave absorption as a function of the isothermal annealing treatment.
Fiber based functional near infra-red (fNIR) spectroscopy has been considered as a cost effective imaging modality. To
achieve a better spatial resolution and greater accuracy in extraction of the optical parameters (i.e., μa and μ's), broadband
frequency modulated systems covering multi-octave frequencies of 10-1000MHz is considered. A helmet mounted
broadband free space fNIR system is considered as significant improvement over bulky commercial fiber fNIR
realizations that are inherently uncomfortable and dispersive for broadband operation. Accurate measurements of
amplitude and phase of the frequency modulated NIR signals (670nm, 795nm, and 850nm) is reported here using free
space optical transmitters and receivers realized in a small size and low cost modules. The tri-wavelength optical
transmitter is based on vertical cavity semiconductor lasers (VCSEL), whereas the sensitive optical receiver is based on
either PIN or APD photodiodes combined with transimpedance amplifiers. This paper also has considered brain
phantoms to perform optical parameter extraction experiments using broadband modulated light for separations of up to
5cm. Analytical models for predicting forward (transmittance) and backward (reflectance) scattering of modulated
photons in diffused media has been modeled using Diffusion Equation (DE). The robustness of the DE modeling and
parameter extraction algorithm was studied by experimental verification of multi-layer diffused media phantoms. In
particular, comparison between analytical and experimental models for narrow band and broadband has been performed
to analyze the advantages of our broadband fNIR system.
Surface enhanced Raman scattering (SERS) is now a well-established technique to greatly amplify the normally weak
Raman scattering signals. The amplification is achieved by using SERS substrates - specially structured metallic
substrates with nano-scale morphological features. One of the most widely used methods for SERS amplification
employs nanoparticles of silver or gold either in colloidal suspension or in dry-drop form. In such substrates SERS
amplification factors (AF) exceeding 1012 have been reported. The reproducibility of the colloid-based substrates,
however, is a problem. The lack of reproducibility can be caused by a variety of factors that can change the interparticle
distances. In this paper we show that thermal annealing of SERS substrates fabricated using commercially available
nano-particle inks can be used to create thermally stable substrates with high reproducibility. It appears that thermal
annealing destroys the unstable hot-spots with very high AF's but still leaves the sample with high AF sites yielding
spatially averaged substrate AF's exceeding 108.
A pilot human study is conducted to evaluate the potential of using diffuse photon density wave (DPDW) methodology at near-infrared (NIR) wavelengths (685 to 830 nm) to monitor changes in tissue hemoglobin concentration in diabetic foot ulcers. Hemoglobin concentration is measured by DPDW in 12 human wounds for a period ranging from 10 to 61 weeks. In all wounds that healed completely, gradual decreases in optical absorption coefficient, oxygenated hemoglobin concentration, and total hemoglobin concentration are observed between the first and last measurements. In nonhealing wounds, the rates of change of these properties are nearly zero or slightly positive, and a statistically significant difference (p<0.05) is observed in the rates of change between healing and nonhealing wounds. Differences in the variability of DPDW measurements over time are observed between healing and nonhealing wounds, and this variance may also be a useful indicator of nonhealing wounds. Our results demonstrate that DPDW methodology with a frequency domain NIR device can differentiate healing from nonhealing diabetic foot ulcers, and indicate that it may have clinical utility in the evaluation of wound healing potential.
Changes of optical properties of wound tissue in hairless rats were quantified by diffuse photon density wave methodology at near-infrared frequencies. The diffusion equation for semi-infinite media was used to calculate the absorption and scattering coefficients based on measurements of phase and amplitude with a frequency domain device. There was an increase in the absorption and scattering coefficients and a decrease in blood saturation of the wounds compared with the nonwounded sites. The changes correlated with the healing stage of the wound. The data obtained were supported by immunohistochemical analysis of wound tissue. These results verified now by two independent animal studies could suggest a noninvasive method to detect the progress of wound healing.
Quantitative non-invasive assessment of the wound healing process in chronic wounds may assist in selection and
monitoring of expensive treatments. The Diffuse Photon Density Wave (DPDW) methodology at near infrared
wavelengths can be used to non-invasively measure the optical absorption and reduced scattering coefficients of tissue at
depths of several millimeters. Changes in the optical properties of tissue at near-infrared wavelengths (685nm-950nm)
are caused by changes in blood volume, oxygenation, and tissue hydration. A four-wavelength DPDW system with a
single source position and four detectors was used to monitor the optical properties of wounds in healthy and
streptozotocin-induced diabetic rats. Optical data obtained after inflicting full-thickness wounds on the dorsal region of
diabetic and control rats indicate that DPDW technology can be used to monitor wound healing and differentiate the rate
of impaired vs. normal wound healing. The concentrations of oxyhemoglobin, deoxyhemoglobin and water were
calculated from the optical absorption coefficients. Changes in hemoglobin concentration may indicate increased
vascularization throughout the wound healing process, while changes in water content may reflect inflammation
following tissue injury. These physiological changes are supported by qualitative immunohistochemical analysis of
wound biopsies.
Raman spectroscopy is now a well-established analytical tool for obtaining rapid and compound specific
information for chemical analysis. However, Raman scattering - inelastic scattering of photons - cross
sections are typically of the order of 10-30 cm2 per molecule and thus Raman signals are usually weak. In
Surface Enhanced Raman Scattering (SERS) the signals can be greatly amplified by using specially
structured metallic (usually Ag, Au, and Cu) substrates. SERS substrates can be fabricated by a variety of
methods. Here, we report a method for fabricating SERS substrates from commercially available silver
nanoparticle based printing inks. For dilute inks (~ 1-2% Ag by weight) the method involves the
airbrushing of inks on heated (~100oC) quartz or polymer substrates followed by heating at 170oC for about
20 minutes. The heating treatment removes the polymer coating used to prevent aggregation of Ag
particles in the colloidal suspension and allows partial sintering of particles. More concentrated inks (~ 20
- 30% Ag by weight) can be applied to various substrates at room temperature followed by the thermal
treatment. SERS spectra of Rhodamine 6G, and β-carotene molecules are reported. SERS amplification
factors of more than 106 can be easily obtained reproducibly.
Little is known about the neurological underpinnings of deliberate deception. Recent advances in the detection of deception have examined brain responses during experimental deception protocols. A consensus has begun to emerge across the handful of functional magnetic resonance imaging (fMRI) studies that have examined deception implicating areas of the dorsolateral and inferior prefrontal cortex as active during deliberate deception. The purpose of the current study was to determine the utility of functional near-infrared spectroscopy (fNIR), a neuroimaging technique that allows reasonable ecological utility, for the detection of deception. Using a modified version of the Guilty Knowledge Task, participants attempted to conceal the identity of a playing card they were holding while dorsolateral and inferior frontal cortices were monitored with fNIR. The results revealed increased activation in bilateral inferior frontal gyri (BA 47/45) and middle frontal gyri (BA 46/10) when participants were lying. The results provide evidence that inferior and middle prefrontal cortical areas are associated at least some forms of deliberate deception. fNIR has the potential to provide a field-deployable brain-based method for the detection of deception.
We report results of our recent efforts to develop nano-tools to study proteins and their interactions in complex environments that exist on the cell membrane and inside the cells. Due to the spatial constraints imposed on the mobility of cell constituents, it is reasonable to expect that the nature and dynamics of the biomolecular interactions in a living cell would be substantially different from those routinely observed in dilute solutions. Nanotechnology has begun to provide tools with which to monitor processes that occur in membranes and intracellular regions. Nano-optics is a rich source of such emerging tools. Tapered optical fibers coated with metallic films can effectively confine excitation light to sub-wavelength linear dimensions and cubic nanometer excitation volumes. This leads not only to a resolution that exceeds the diffraction-limited values, but also to the elimination of the background signal. Thus, highly localized and specific regions of cellular function can be investigated. By immobilizing silver colloidal nanoparticles on such tapered fibers we have also fabricated surface enhanced Raman scattering (SERS) probes. Nanoprobes have been found to enable detection of fluorescent antibody molecules immobilized on a functionalized glass surface and polychromic quantum dots in picomolar solutions. In addition, we have successfully inserted nanoprobes with dimensions of 30-80 nm into both adherent insect and mammalian cells with maintenance of their viability. We summarize our development of optical nanoprobes with the motivation to detect cell-surface and intracellular proteins of the interleukin-5 system in native cellular environments, through quantum dot fluorescence and SERS.
This paper summarizes the design steps that are followed during the development of the portable optical imager for breast cancer screening. The design steps considered the parameters such as total power consumption versus battery weight and size, speed of data acquisition versus cost and complexity of the design (functionality), graphical display versus operating system choice. We have used a single board computer system that uses Windows CE as the real time operating system. This choice was preferred since our graphical display requirements can only be carried out with the CE environment's GUI kernels.
The dielectric and magnetic influence on human cells have been widely studied previously by the authors. Recently, the effects of energy in the visible electromagnetic spectrum have been investigated. In this subsequent study, the photonic effects on the in vitro migration of the polymorphonuclear and mononuclear leukocytes are compared with the corresponding electromagnetic field effects. Dielectric spectra of the polymorph in the 300 KHz to 400 KHz and 700 KHz to 800 KHz range have been measured. At frequencies of 350 KHz and 720 KHz an increase in the migration of the polymorphonuclear leukocyte have been observed. This stimulation was attributed to the charges on the nuclear surface. Recent preliminary data have shown a similar increased migration in the 20 MHz range. Photonic studies have indicated an enhanced migration for the polymorphonuclear leukocytes at a wavelength of 660 nm (red) and an inhibited migration at 565 nm (green). The photonic effects were postulated to be the results of a biochemical interaction rather than a membranous surface charge displacement secondary to an electric field. The migration of the white blood cells were measurement via the Boyden chamber technique and expressed in terms of a cytokinetic index which expresses the cellular movement independent of its environmental concentration gradient.
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