Source-detector Separation Research Articles

In vivo time-gated diffuse correlation spectroscopy at quasi-null source-detector separation

We demonstrate time domain diffuse correlation spectroscopy at quasi-null source-detector separation by using a fast time-gated single-photon avalanche diode without the need of time-tagging electronics. This approach allows for increased photon collection, simplified real-time instrumentation, and reduced probe dimensions. Depth discriminating, quasi-null distance measurement of blood flow in a human subject is presented. We envision the miniaturization and integration of matrices of optical sensors of increased spatial resolution and the enhancement of the contrast of local blood flow changes.

Highly parallel, interferometric diffusing wave spectroscopy for monitoring cerebral blood flow dynamics.

Light-scattering methods are widely used in soft matter physics and biomedical optics to probe dynamics in turbid media, such as diffusion in colloids or blood flow in biological tissue. These methods typically rely on fluctuations of coherent light intensity, and therefore cannot accommodate more than a few modes per detector. This limitation has hindered efforts to measure deep tissue blood flow with high speed, since weak diffuse light fluxes, together with low single-mode fiber throughput, result in low photon count rates. To solve this, we introduce multimode fiber (MMF) interferometry to the field of diffuse optics. In doing so, we transform a standard complementary metal-oxide-semiconductor (CMOS) camera into a sensitive detector array for weak light fluxes that probe deep in biological tissue. Specifically, we build a novel CMOS-based, multimode interferometric diffusing wave spectroscopy (iDWS) system and show that it can measure ∼20 speckles simultaneously near the shot noise limit, acting essentially as ∼20 independent photon-counting channels. We develop a matrix formalism, based on MMF mode field solutions and detector geometry, to predict both coherence and speckle number in iDWS. After validation in liquid phantoms, we demonstrate iDWS pulsatile blood flow measurements at 2.5 cm source-detector separation in the adult human brain in vivo. By achieving highly sensitive and parallel measurements of coherent light fluctuations with a CMOS camera, this work promises to enhance performance and reduce cost of diffuse optical instruments.

Diffuse near-infrared imaging of tissue with picosecond time resolution.

Optical imaging of biological tissue in vivo at multiple wavelengths in the near-infrared (NIR) spectral range can be achieved with picosecond time resolution at high sensitivity by time-correlated single photon counting. Measuring and analyzing the distribution of times of flight of photons randomly propagated through the tissue has been applied for diffuse optical imaging and spectroscopy, e.g. of human breast tissue and of the brain. In this article, we review the main features and the potential of NIR multispectral imaging with picosecond time resolution and illustrate them by exemplar applications in these fields. In particular, we discuss the experimental methods developed at the Physikalisch-Technische Bundesanstalt (PTB) to record optical mammograms and to quantify the absorption and scattering properties from which hemoglobin concentration and oxygen saturation of healthy and diseased breast tissue have been derived by combining picosecond time-domain and spectral information. Furthermore, optical images of functional brain activation were obtained by a non-contact scanning device exploiting the null source-detector separation approach which takes advantage of the picosecond time resolution as well. The recorded time traces of changes in the oxy- and deoxyhemoglobin concentrations during a motor stimulation investigation show a localized response from the brain.

Multi-distance diffuse optical spectroscopy with a single optode via hypotrochoidal scanning.

Frequency-domain diffuse optical spectroscopy (FD-DOS) is an established technique capable of determining optical properties and chromophore concentrations in biological tissue. Most FD-DOS systems use either manually positioned, handheld probes or complex arrays of source and detector fibers to acquire data from many tissue locations, allowing for the generation of 2D or 3D maps of tissue. Here, we present a new method to rapidly acquire a wide range of source-detector (SD) separations by mechanically scanning a single SD pair. The source and detector fibers are mounted on a scan head that traces a hypotrochoidal pattern over the sample that, when coupled with a high-speed FD-DOS system, enables the rapid collection of dozens of SD separations for depth-resolved imaging. We demonstrate that this system has an average error of 4±2.6% in absorption and 2±1.8% in scattering across all SD separations. Additionally, by linearly translating the device, the size and location of an absorbing inhomogeneity can be determined through the generation of B-scan images in a manner conceptually analogous to ultrasound imaging. This work demonstrates the potential of single optode diffuse optical scanning for depth resolved visualization of heterogeneous biological tissues at near real-time rates.

Performance comparison of the MOXY and PortaMon near-infrared spectroscopy muscle oximeters at rest and during exercise.

The purpose of the study was to compare muscle oxygenation as measured by two portable, wireless near-infrared spectroscopy (NIRS) devices under resting and dynamic conditions. A recently developed low-cost NIRS device (MOXY) was compared against an established PortaMon system that makes use of the spatially resolved spectroscopy algorithm. The influence of increasing external pressure on tissue oxygen saturation index (TSI) indicated that both devices are stable between 2 and 20mmHg. However, above this pressure, MOXY reports declining TSI values. Analysis of adipose tissue thickness (ATT) and TSI shows a significant, nonlinear difference between devices at rest. The devices report similar TSI (%) values at a low ATT (<7 mm) (PortaMon minus MOXY difference is +1.1±2.8%) with the major subsequent change between the devices occurring between 7 and 10mm; at ATT values >10 mm the difference remains constant (-14.7±2.8%). The most likely explanation for this difference is the small source-detector separation (2.5cm) in the MOXY resulting in lower tissue penetration into muscle in subjects with higher ATT. Interday test-retest reliability of resting TSI was evaluated on five separate occasions, with the PortaMon reporting a lower coefficient of variation (1.8% to 2.5% versus 5.7% to 6.2%). In studies on male subjects with low ATT, decreases in the TSI were strongly correlated during isometric exercise, arterial occlusion, and incremental arm crank exercise. However, the MOXY reports a greater dynamic range, particularly during ischemia induced by isometric contraction or occlusion (Δ74.3% versus Δ43.7%; hyperemia MAX-occlusion MIN). This study shows that in this subject group both MOXY and PortaMon produce physiologically credible TSI measures during rest and exercise. However, the absolute values obtained during exercise are generally not comparable between devices unless corrected by physiological calibration following an arterial occlusion.

Quantitative evaluation of functional Near Infrared Spectroscopy measurements with different source-detector separations using Monte Carlo simulation

Quantitative evaluation of functional Near Infrared Spectroscopy measurements with different source-detector separations using Monte Carlo simulation

Investigation of light propagation and detection in human head for realistic settings under clinical conditions

Investigation of light propagation and detection in human head for realistic settings under clinical conditions

Performance enhancement of a brain-computer interface using high-density multi-distance NIRS

This study investigated the effectiveness of using a high-density multi-distance source-detector (SD) separations in near-infrared spectroscopy (NIRS), for enhancing the performance of a functional NIRS (fNIRS)-based brain-computer interface (BCI). The NIRS system that was used for the experiment was capable of measuring signals from four SD separations: 15, 21.2, 30, and 33.5 mm, and this allowed the measurement of hemodynamic response alterations at various depths. Fifteen participants were asked to perform mental arithmetic and word chain tasks, to induce task-related hemodynamic response variations, or they were asked to stay relaxed to acquire a baseline signal. To evaluate the degree of BCI performance enhancement by high-density channel configuration, the classification accuracy obtained using a typical low-density lattice SD arrangement, was compared to that obtained using the high-density SD arrangement, while maintaining the SD separation at 30 mm. The analysis results demonstrated that the use of a high-density channel configuration did not result in a noticeable enhancement of classification accuracy. However, the combination of hemodynamic variations, measured by two multi-distance SD separations, resulted in the significant enhancement of overall classification accuracy. The results of this study indicated that the use of high-density multi-distance SD separations can likely provide a new method for enhancing the performance of an fNIRS-BCI.

Evaluation of a pointwise microcirculation assessment method using liquid and multilayered tissue simulating phantoms.

.A fiber-optic probe-based instrument, designed for assessment of parameters related to microcirculation, red blood cell tissue fraction (), oxygen saturation (), and speed resolved perfusion, has been evaluated using state-of-the-art tissue phantoms. The probe integrates diffuse reflectance spectroscopy (DRS) at two source–detector separations and laser Doppler flowmetry, using an inverse Monte Carlo method for identifying the parameters of a multilayered tissue model. Here, we characterize the accuracy of the DRS aspect of the instrument using (1) liquid blood phantoms containing yeast and (2) epidermis-dermis mimicking solid-layered phantoms fabricated from polydimethylsiloxane, titanium oxide, hemoglobin, and coffee. The root-mean-square (RMS) deviations for for the two liquid phantoms were 11% and 5.3%, respectively, and 11% for the solid phantoms with highest hemoglobin signatures. The RMS deviation for was 5.2% and 2.9%, respectively, for the liquid phantoms, and 2.9% for the solid phantoms. RMS deviation for the reduced scattering coefficient (), for the solid phantoms was 15% (475 to 850 nm). For the liquid phantoms, the RMS deviation in average vessel diameter () was . In conclusion, the skin microcirculation parameters and , as well as, and are estimated with reasonable accuracy.

Freehand diffuse optical spectroscopy imaging for intraoperative identification of major venous and arterial vessels underlying peritoneal fat: an in vivo demonstration in a pig model.

Inadvertent injury to important anatomic structures is a significant risk in minimally invasive surgery (MIS) that potentially requires conversion to an open procedure, which results in increased morbidity and mortality. Surgeons operating minimal-invasively currently do not have an easy-to-use, real-time device to aid in intraoperative identification of important anatomic structures that underlie tissue planes. We demonstrate freehand diffuse optical spectroscopy (DOS) imaging for intraoperatively identifying major underlying veins and arteries. An applicator probe that can be affixed to and detached from an 8-mm laparoscopic instrument has been developed. The 10-mm DOS source-detector separation renders sampling of tissue heterogeneities a few millimeters deep. DOS spectra acquired consecutively during freehand movement of the applicator probe on the tissue surface are displayed as a temporal and spectral image to assist in spatially resolved identification of the underlying structures. Open surgery identifications of the vena cava and aorta underlying peritoneal fat of ∼4 mm in thickness using the applicator probe under room light were demonstrated repeatedly in multiple pigs in vivo.

Determination of optical properties of turbid medium from relative interstitial CW radiance measurements using the incomplete P3 approximation.

Interstitial determination of the tissue optical properties is important in biomedicine, especially for interstitial laser therapies. Continuous wave (CW) radiance techniques which examine light from multiple directions have been proposed as minimally invasive methods for determining the optical properties under an interstitial probe arrangement. However, both the fitting algorithm based on the P3 approximation and the analytical method based on the diffusion approximation (DA), which are currently used recovery algorithms, cannot extract the optical properties of tissue with low transport albedos accurately from radiance measurements. In this paper, we proposed an incomplete P3 approximation for the radiance, the P3in for short, which is the asymptotic part of the solution for the P3 approximation. The relative differences between the P3in and the P3 were within 0.48% over a wide range of clinically relevant optical properties for measurements at source detector separations (SDS) from 5 mm to 10 mm and angles from 0° to 160°. Based on the P3in, we developed an analytical method for extracting the optical properties directly using simple expressions constructed from the radiance measurements at only two SDSs and four angles. The developed recovery algorithm was verified by simulated and experimental radiance data. The results show that both the absorption and reduced scattering coefficients were recovered accurately with relative errors within 5.28% and 3.86%, respectively, from the simulated data and with relative errors within 10.82% and 10.67%, respectively, from the experimental data over a wide range of albedos from 0.5 to 0.99. Since the developed P3in-based radiance technique can obtain the optical properties rapidly from the measurements at only two SDSs and four angles, it is expected to be used for in vivo and in situ determination of the optical properties in online treatment planning during laser therapies.

Detection of precancerous lesions in the oral cavity using oblique polarized reflectance spectroscopy: a clinical feasibility study.

.We developed a multifiber optical probe for oblique polarized reflectance spectroscopy (OPRS) in vivo and evaluated its performance in detection of dysplasia in the oral cavity. The probe design allows the implementation of a number of methods to enable depth resolved spectroscopic measurements including polarization gating, source–detector separation, and differential spectroscopy; this combination was evaluated in carrying out binary classification tasks between four major diagnostic categories: normal, benign, mild dysplasia (MD), and severe dysplasia (SD). Multifiber OPRS showed excellent performance in the discrimination of normal from benign, MD, SD, and MD plus SD yielding sensitivity/specificity values of 100%/93%, 96%/95%, 100%/98%, and 100%/100%, respectively. The classification of benign versus dysplastic lesions was more challenging with sensitivity and specificity values of 80%/93%, 71%/93%, and 74%/80% in discriminating benign from SD, MD, and SD plus MD categories, respectively; this challenge is most likely associated with a strong and highly variable scattering from a keratin layer that was found in these sites. Classification based on multiple fibers was significantly better than that based on any single detection pair for tasks dealing with benign versus dysplastic sites. This result indicates that the multifiber probe can perform better in the detection of dysplasia in keratinized tissues.

Probe for evaluating the absorbing and transport scattering properties of turbid fluids using low-cost time-of-flight technology.

A probe is described that when immersed into a highly scattering fluid provides a measurement of its scattering and absorbing properties at a single optical wavelength. It uses recently available low-cost proximity sensor modules to estimate the mean flight times of photons diffusely transmitted between near-infrared sources and detectors at two different separations. The probe has been designed with a specific application for enabling the rapid and efficient production of fluids, which mimic the optical properties of biological tissues. The potential of the device is demonstrated using precalibrated solutions of intralipid, an intravenous nutrient, and absorbing dye. It is shown that a combination of time-of-flight measurements at two source–detector separations can uniquely specify the absorption coefficient and the transport scattering coefficient.

Modeling subdiffusive light scattering by incorporating the tissue phase function and detector numerical aperture

To detect small-scale changes in tissue with optical techniques, small sampling volumes and, therefore, short source–detector separations are required. In this case, reflectance measurements are not adequately described by the diffusion approximation. Previous studies related subdiffusive reflectance to ? or ? , which parameterize the phase function. Recently, it was demonstrated that ? predicts subdiffusive reflectance better than ? , and that ? becomes less predictive for lower numerical apertures (NAs). We derive and evaluate the parameter R p NA , which incorporates the NA of the detector and the integral of the phase function over the NA in the backward and forward directions. Monte Carlo simulations are performed for overlapping source/detector geometries for a range of phase functions, reduced scattering coefficients, NAs, and source/detector diameters. R p NA improves prediction of the measured reflectance compared to ? and ? . It is, therefore, expected that R p NA will improve derivation of optical properties from subdiffusive measurements.

Structured illumination diffuse optical tomography for noninvasive functional neuroimaging in mice.

Optical intrinsic signal (OIS) imaging has been a powerful tool for capturing functional brain hemodynamics in rodents. Recent wide field-of-view implementations of OIS have provided efficient maps of functional connectivity from spontaneous brain activity in mice. However, OIS requires scalp retraction and is limited to superficial cortical tissues. Diffuse optical tomography (DOT) techniques provide noninvasive imaging, but previous DOT systems for rodent neuroimaging have been limited either by sparse spatial sampling or by slow speed. Here, we develop a DOT system with asymmetric source-detector sampling that combines the high-density spatial sampling (0.4mm) detection of a scientific complementary metal-oxide-semiconductor camera with the rapid (2Hz) imaging of a few ([Formula: see text]) structured illumination (SI) patterns. Analysis techniques are developed to take advantage of the system's flexibility and optimize trade-offs among spatial sampling, imaging speed, and signal-to-noise ratio. An effective source-detector separation for the SI patterns was developed and compared with light intensity for a quantitative assessment of data quality. The light fall-off versus effective distance was also used for in situ empirical optimization of our light model. We demonstrated the feasibility of this technique by noninvasively mapping the functional response in the somatosensory cortex of the mouse following electrical stimulation of the forepaw.

Adopting higher-order similarity relations for improved estimation of optical properties from subdiffusive reflectance.

Estimation of optical properties from subdiffusive reflectance acquired at short source-detector separations is challenging due to the sensitivity to the underlying scattering phase function. In recent studies, a second-order similarity parameter γ has been increasingly used alongside the absorption and reduced scattering coefficients to account for some of the phase function variability. By using Monte Carlo simulations, we show that the influence of the scattering phase function on the subdiffusive reflectance for the biologically relevant variations can be captured sufficiently well by considering γ and a third-order similarity parameter δ. Utilizing this knowledge, we construct an inverse model that estimates the absorption and reduced scattering coefficients, γ and δ, from spatially resolved reflectance. Nearly an order of magnitude smaller errors of the estimated optical properties are obtained in comparison to the inverse model that only composes γ.

Probing depth in diffuse optical spectroscopy and structured illumination imaging: a Monte Carlo study

Diffuse optical spectroscopy (DOS) and its modification employing structured illumination are widely used in monitoring biotissue oxygenation. In such measurements it is important to know the probing volume for definite source-detector configuration; however, it cannot be measured directly. Monte Carlo simulations allow to trace the probing depth of each individual photon contributing to the signal, which provides a numerical solution for this problem. In this study we investigate distributions of photons over maximal depth reached in turbid media (probing depth) with optical parameters typical for cutaneous tissues at the wavelength of 600 nm. Different configurations of probing illumination are considered, such as collimated point source, one-dimension sinusoidal and rectangular patterns. For collimated point source and zero source-detector separation the number of collected photons monotonously decreases with the probing depth while a pronounced maximum in the distribution is manifested with the increase of source-detector separation. The position of this maximum shifts to higher depths with the decrease of µ a . For one-direction sinusoidal and rectangular illumination patterns it is shown that when the photons are collected near the center of a bright stripe, the peak of the distribution remains close to the surface. When the photons are collected near the center of a dark stripe the peak shifts towards higher depths with the decrease in spatial duty cycle and spatial frequency of the illumination pattern. Employment of rectangular illumination pattern seems more efficient for DOS applications due to wider abilities for controlling probing depth.

Functional NIRS Measurement of Cytochrome-C-Oxidase Demonstrates a More Brain-Specific Marker of Frontal Lobe Activation Compared to the Haemoglobins.

Functional near-infrared spectroscopy (fNIRS) is an increasingly common neuromonitoring technique used to observe evoked haemodynamic changes in the brain in response to a stimulus. The measurement is typically in terms of concentration changes of oxy- (∆HbO2) and deoxy- (∆HHb) haemoglobin. However, noise from systemic fluctuations in the concentration of these chromophores can contaminate stimulus-evoked haemodynamic responses, leading to misinterpretation of results. Short-separation channels can be used to regress out extracerebral haemodynamics to better reveal cerebral changes, significantly improving the reliability of fNIRS. Broadband NIRS can be used to additionally monitor concentration changes of the oxidation state of cytochrome-c-oxidase (∆oxCCO). Recent studies have shown ∆oxCCO to be a depth-dependent and hence brain-specific signal. This study aims to investigate whether ∆oxCCO can produce a more robust marker of functional activation. Continuous frontal lobe NIRS measurements were collected from 17 healthy adult volunteers. Short 1 cm source-detector separation channels were regressed from longer separation channels in order to minimise the extracerebral contribution to standard fNIRS channels. Significant changes in ∆HbO2 and ∆HHb were seen at 1 cm channels but were not observed in ∆oxCCO. An improvement in the haemodynamic signals was achieved with regression of the 1 cm channel. Broadband NIRS-measured concentration changes of the oxidation state of cytochrome-c-oxidase has the potential to be an alternative and more brain-specific marker of functional activation.

Functional imaging of the human brain using a modular, fibre-less, high-density diffuse optical tomography system.

We present the first three-dimensional, functional images of the human brain to be obtained using a fibre-less, high-density diffuse optical tomography system. Our technology consists of independent, miniaturized, silicone-encapsulated DOT modules that can be placed directly on the scalp. Four of these modules were arranged to provide up to 128, dual-wavelength measurement channels over a scalp area of approximately 60 × 65 mm2. Using a series of motor-cortex stimulation experiments, we demonstrate that this system can obtain high-quality, continuous-wave measurements at source-detector separations ranging from 14 to 55 mm in adults, in the presence of hair. We identify robust haemodynamic response functions in 5 out of 5 subjects, and present diffuse optical tomography images that depict functional haemodynamic responses that are well-localized in all three dimensions at both the individual and group levels. This prototype modular system paves the way for a new generation of wearable, wireless, high-density optical neuroimaging technologies.

Estimation of optical properties by spatially resolved reflectance spectroscopy in the subdiffusive regime.

We propose and objectively evaluate an inverse Monte Carlo model for estimation of absorption and reduced scattering coefficients and similarity parameter ? from spatially resolved reflectance (SRR) profiles in the subdiffusive regime. The similarity parameter ? carries additional information on the phase function that governs the angular properties of scattering in turbid media. The SRR profiles at five source-detector separations were acquired with an optical fiber probe. The inverse Monte Carlo model was based on a cost function that enabled robust estimation of optical properties from a few SRR measurements without a priori knowledge about spectral dependencies of the optical properties. Validation of the inverse Monte Carlo model was performed on synthetic datasets and measured SRR profiles of turbid phantoms comprising molecular dye and polystyrene microspheres. We observed that the additional similarity parameter ? substantially reduced the reflectance variability arising from the phase function properties and significantly improved the accuracy of the inverse Monte Carlo model. However, the observed improvement of the extended inverse Monte Carlo model was limited to reduced scattering coefficients exceeding ?15??cm?1, where the relative root-mean-square errors of the estimated optical properties were well within 10%.