We present a multimodal approach using functional near-infrared spectroscopy (fNIRS) and optically pumped magnetometers (OPM) for imaging neurovascular coupling (NVC). The study aims to achieve high-density imaging by combining state-of-the-art implementation of the techniques. In-vivo studies during a motor cortex stimulation were carried out inside the 7-layer magnetically shielded room BMSR2 - the single most magnetically-shielded room on Earth. The study demonstrates the feasibility of the proposed approach and paves the way for future mapping and tomography reconstructions using magnetic and optical data.
Significance: Multi-laboratory initiatives are essential in performance assessment and standardization—crucial for bringing biophotonics to mature clinical use—to establish protocols and develop reference tissue phantoms that all will allow universal instrument comparison.
Aim: The largest multi-laboratory comparison of performance assessment in near-infrared diffuse optics is presented, involving 28 instruments and 12 institutions on a total of eight experiments based on three consolidated protocols (BIP, MEDPHOT, and NEUROPT) as implemented on three kits of tissue phantoms. A total of 20 synthetic indicators were extracted from the dataset, some of them defined here anew.
Approach: The exercise stems from the Innovative Training Network BitMap funded by the European Commission and expanded to include other European laboratories. A large variety of diffuse optics instruments were considered, based on different approaches (time domain/frequency domain/continuous wave), at various stages of maturity and designed for different applications (e.g., oximetry, spectroscopy, and imaging).
Results: This study highlights a substantial difference in hardware performances (e.g., nine decades in responsivity, four decades in dark count rate, and one decade in temporal resolution). Agreement in the estimates of homogeneous optical properties was within 12% of the median value for half of the systems, with a temporal stability of <5 % over 1 h, and day-to-day reproducibility of <3 % . Other tests encompassed linearity, crosstalk, uncertainty, and detection of optical inhomogeneities.
Conclusions: This extensive multi-laboratory exercise provides a detailed assessment of near-infrared Diffuse optical instruments and can be used for reference grading. The dataset—available soon in an open data repository—can be evaluated in multiple ways, for instance, to compare different analysis tools or study the impact of hardware implementations.
Time-domain diffuse correlation spectroscopy (TD-DCS) is a non-invasive optical technique, which measures tissue blood flow with path-length resolution. Ideally, this technique requires a pulsed laser with an adequate illumination power, a long coherence length, and a narrow instrument response function (IRF), while available laser modules cannot satisfy all these conditions. We systematically characterized three pulsed laser sources and compared their performances using phantom and in vivo measurements. We found that each laser has the potential to be used in TD-DCS applications. Also, the effects caused by the IRF are more significant than the effect of the limited coherence length.
The effect of hemoglobin spectra on quantification of concentrations of oxy-, deoxyhemoglobin, and oxygen saturation were studied using multi-wavelength time-domain NIRS measurements performed on a series of blood-lipid phantoms.
Time-domain diffuse optics exploits near infrared light pulses diffused in turbid samples to retrieve their optical properties e.g., absorption and reduced scattering coefficients. Typically, interference effect are discarded, but speckle effects are exploited in other techniques e.g., diffuse correlation spectroscopy (DCS) to retrieve information regarding the tissue dynamics. Here, using a highly coherent Ti:Sapphire mode-locked laser and a single-mode detection fiber, we report the direct observation of temporal fluctuations in the measured distribution of time-of-flights (DTOF) curve. We study the dependence of these fluctuations on the sample dynamical properties (moving from fluid to rigid tissue-mimicking phantoms) and on the area of the detection fiber, which is directly linked to the number of collected coherence areas. Our observation agree with a time-resolved speckle pattern, and may enable the simultaneous monitoring of the tissue optical and dynamical properties.
Performance assessment and standardization are indispensable for instruments of clinical relevance in general and clinical instrumentation based on photon migration/diffuse optics in particular. In this direction, a multi-laboratory exercise was initiated with the aim of assessing and comparing their performances. 29 diffuse optical instruments belonging to 11 partner institutions of a European level Marie Curie Consortium BitMap1 were considered for this exercise. The enrolled instruments covered different approaches (continuous wave, CW; frequency domain, FD; time domain, TD and spatial frequency domain imaging, SFDI) and applications (e.g. mammography, oximetry, functional imaging, tissue spectroscopy). 10 different tests from 3 well-accepted protocols, namely, the MEDPHOT2 , the BIP3 , and the nEUROPt4 protocols were chosen for the exercise and the necessary phantoms kits were circulated across labs and institutions enrolled in the study. A brief outline of the methodology of the exercise is presented here. Mainly, the design of some of the synthetic descriptors, (single numeric values used to summarize the result of a test and facilitate comparison between instruments) for some of the tests will be discussed.. Future actions of the exercise aim at deploying these measurements onto an open data repository and investigating common analysis tools for the whole dataset.
We utilized time-domain diffuse correlation spectroscopy (TD-DCS) to quantify depth-resolved blood flow changes for in vivo experiments on arm and forehead adult humans. We illustrated that conventional TD-DCS processing is incapable of estimating blood flow changes at short source-detector separations, as expected. To tackle this problem, we introduced a novel model. We recovered the relative blood flow index of the forearm muscle during the cuff occlusion challenge and human forehead under variable pressure accurately.
We apply time-domain diffuse correlation spectroscopy (TD DCS) to quantify dynamics in samples with mixed dynamics, containing both static and dynamic scatterers. We demonstrate that standard TD DCS processing is incapable to properly quantify dynamics at short source-detector distances due to the strong influence of the static component. To solve this problem, we introduce a novel model, which allows recovering the autocorrelation decay of the dynamic part properly. We then apply this novel approach in humans in vivo. We recovered the blood flow index of the leg muscle covered by the thin static turbid layer during the cuff occlusion challenge.
Performance assessment of instruments is a growing demand in the diffuse optics community and there is a definite need to get together to address this issue. Within the EU Network BITMAP1, we initiated a campaign for the performance evaluation of 10 diffuse optical instrumentation from 7 partner institutions adopting a set of 3 well accepted, standardized protocols. A preliminary analysis of the outcome along with future perspectives will be presented.
We have studied experimentally and theoretically spatial distributions of factors describing sensitivity of the statistical moments of distributions of times of flight (DTOFs) of photons penetrating through the medium to changes in absorption coefficient. Additionally, the moments subtraction procedure, based on difference between statistical moments measured at two interoptode distances was applied in order to modify the sensitivity profiles.
Open Data philosophy is becoming more popular among scientists. Open Data approach aims to transform science by making high-quality and well-documented scientific data open to everybody in order to promote collaboration and transparency. In diffuse optical and near-infrared spectroscopy community, a large measurement dataset collected with state-of-the-art instrumentation applied on well-defined phantoms is still missing. Within that context, several European labs from BitMap network1 have collected diffuse optical data on standard phantoms involving the largest set of diffuse optics instruments published until now. In this work, we present a running project on the open dataset and associated reporting tools.
We apply time-domain diffuse correlation spectroscopy (TD DCS) to quantify dynamics in a two-layer turbid phantom, where the top layer contains purely static, while bottom layer contains only dynamic scatterers. We demonstrate that the standard TD DCS processing is incapable to properly quantify dynamics at short sourcedetector distances (<1 cm) due to strong influence of the static layer. To solve this problem we introduce a novel model accompanied by the numerical noise-correction, which allows to properly recover the autocorrelation decay of the dynamic homogeneous medium hidden by the static turbid layer. Our approach can be thus beneficial for DCS applications in samples with mixed dynamics.
We present results of clinical studies in patients during increase in intra-abdominal pressure (IAP). Changes in brain hemoglobin concentration assessed from time-resolved nearinfrared spectroscopy system were analyzed in frequency domain. The amplitude of power spectral density in respiratory band increases while IAP increases what is related to reduced venous outflow.
Absolute concentrations of oxyhaemoglobin and deoxyhaemoglobin obtained using multi-wavelength measurements of time-resolved diffuse reflectance signals are presented. The aim was to test how accurately the concentration of oxy- and deoxyhemoglobin can be measured simultaneously at multiple wavelengths. The optical signals were collected using the system constructed by the author’s groupa , which records the distribution in time of flight of photons (DTOFs) simultaneously at 16 spectral channels ranging from 650 to 850 nm. The measurements were carried out on liquid phantoms containing intralipid solution, human blood and yeast in varying amounts. The oxygen saturation of blood covered a continuous range from 100 % to 0 % during 6 deoxygenation cycles. The estimated values of total haemoglobin (20.9, 35.7, 57.3, 45.7 μM) are close to the reference values obtained using a blood gas analyzer (21.3, 37.0, 57.3, 48.0 μM) and the estimated values of absolute concentrations of oxy-, deoxyand total haemoglobin are similar to the values obtained using a commercial frequency-domain NIRS system (OxiplexTS TM ). The phantom measurements have shown the capability to measure the absolute concentrations of chromophores in a studied media using multi-wavelength, time-resolved NIRS technique. The excess number of spectral channels can potentially be used to resolve changes in oxidation state of cytochrome-c-oxidase enzyme.
The aim of the study was to determine optimal measurement conditions for assessment of brain perfusion with the use of optical contrast agent and time-resolved diffuse reflectometry in the near-infrared wavelength range. The source-detector separation at which the distribution of time of flights (DTOF) of photons provided useful information on the inflow of the contrast agent to the intracerebral brain tissue compartments was determined. Series of Monte Carlo simulations was performed in which the inflow and washout of the dye in extra- and intracerebral tissue compartments was modeled and the DTOFs were obtained at different source-detector separations. Furthermore, tests on diffuse phantoms were carried out using a time-resolved setup allowing the measurement of DTOFs at 16 source-detector separations. Finally, the setup was applied in experiments carried out on the heads of adult volunteers during intravenous injection of indocyanine green. Analysis of statistical moments of the measured DTOFs showed that the source-detector separation of 6 cm is recommended for monitoring of inflow of optical contrast to the intracerebral brain tissue compartments with the use of continuous wave reflectometry, whereas the separation of 4 cm is enough when the higher-order moments of DTOFs are available.
The nEUROPt protocol is one of two new protocols developed within the European project nEUROPt to characterize the performances of time-domain systems for optical imaging of the brain. It was applied in joint measurement campaigns to compare the various instruments and to assess the impact of technical improvements. This protocol addresses the characteristic of optical brain imaging to detect, localize, and quantify absorption changes in the brain. It was implemented with two types of inhomogeneous liquid phantoms based on Intralipid and India ink with well-defined optical properties. First, small black inclusions were used to mimic localized changes of the absorption coefficient. The position of the inclusions was varied in depth and lateral direction to investigate contrast and spatial resolution. Second, two-layered liquid phantoms with variable absorption coefficients were employed to study the quantification of layer-wide changes and, in particular, to determine depth selectivity, i.e., the ratio of sensitivities for deep and superficial absorption changes. We introduce the tests of the nEUROPt protocol and present examples of results obtained with different instruments and methods of data analysis. This protocol could be a useful step toward performance tests for future standards in diffuse optical imaging.
Performance assessment of instruments devised for clinical applications is of key importance for validation and quality assurance. Two new protocols were developed and applied to facilitate the design and optimization of instruments for time-domain optical brain imaging within the European project nEUROPt. Here, we present the “Basic Instrumental Performance” protocol for direct measurement of relevant characteristics. Two tests are discussed in detail. First, the responsivity of the detection system is a measure of the overall efficiency to detect light emerging from tissue. For the related test, dedicated solid slab phantoms were developed and quantitatively spectrally characterized to provide sources of known radiance with nearly Lambertian angular characteristics. The responsivity of four time-domain optical brain imagers was found to be of the order of 0.1 m2 sr. The relevance of the responsivity measure is demonstrated by simulations of diffuse reflectance as a function of source-detector separation and optical properties. Second, the temporal instrument response function (IRF) is a critically important factor in determining the performance of time-domain systems. Measurements of the IRF for various instruments were combined with simulations to illustrate the impact of the width and shape of the IRF on contrast for a deep absorption change mimicking brain activation.
Novel protocols were developed and applied in the European project “nEUROPt” to assess and compare the performance
of instruments for time-domain optical brain imaging and of related methods of data analysis. The objective of the first
protocol, “Basic Instrumental Performance”, was to record relevant basic instrumental characteristics in a direct way.
The present paper focuses on the second novel protocol (“nEUROPt” protocol) that was devoted to the assessment of
sensitivity, spatial resolution and quantification of absorption changes within inhomogeneous media. It was implemented
with liquid phantoms based on Intralipid and ink, with black inclusions and, alternatively, in two-layered geometry.
Small black cylinders of various sizes were used to mimic small localized changes of the absorption coefficient. Their
position was varied in depth and lateral direction to address contrast and spatial resolution. Two-layered liquid phantoms
were used, in particular, to determine depth selectivity, i.e. the ratio of contrasts due to a deep and a superficial
absorption change of the same magnitude. We introduce the tests of the “nEUROPt” protocol and present exemplary
results obtained with various instruments. The results are related to measurements with both types of phantoms and to
the analysis of measured time-resolved reflectance based on time windows and moments. Results are compared for the
different instruments or instrumental configurations as well as for the methods of data analysis. The nEUROPt protocol
is also applicable to cw or frequency-domain instruments and could be useful for designing performance tests in future
standards in diffuse optical imaging.
Recent studies have shown that time-resolved optical measurements of the head can estimate changes in the absorption coefficient with depth discrimination. Thus, changes in tissue oxygenation, which are specific to intracranial tissues, can be assessed using this advanced technique, and this method allows us to avoid the influence of changes to extracerebral tissue oxygenation on the measured signals. We report the results of time-resolved optical imaging that was carried out during carotid endarterectomy. This surgery remains the "gold standard" treatment for carotid stenosis, and intraoperative brain oxygenation monitoring may improve the safety of this procedure. A time-resolved optical imager was utilized within the operating theater. This instrument allows for the simultaneous acquisition of 32 distributions of the time-of-flight of photons at two wavelengths on both hemispheres. Analysis of the statistical moments of the measured distributions of the time-of-flight of photons was applied for estimating changes in the absorption coefficient as a function of depth. Time courses of changes in oxy- and deoxyhemoglobin of the extra- and intracerebral compartments during cross-clamping of the carotid arteries were obtained. A decrease in the oxyhemoglobin concentration and an increase in the deoxyhemoglobin concentrations were observed in a large area of the head. Large changes were observed in the hemisphere ipsilateral to the site of clamped carotid arteries. Smaller amplitude changes were noted at the contralateral site. We also found that changes in the hemoglobin signals, as estimated from intracerebral tissue, are very sensitive to clamping of the internal carotid artery, whereas its sensitivity to clamping of the external carotid artery is limited. We concluded that intraoperative multichannel measurements allow for imaging of brain tissue hemodynamics. However, when monitoring the brain during carotid surgery, a single-channel measurement may be sufficient.
We study fluorescence lifetime of indocyanine green (ICG) using femtosecond laser and sensitive detection based on time-correlated single-photon counting. A time-resolved multichannel spectral system is constructed and applied for determination of the fluorescence lifetime of the ICG in different solvents. Emission properties of ICG in water, milk, and 1% intralipid solution are investigated. Fluorescence of the fluorophore of different concentrations (in a range of 1.7-160 μM) dissolved in different solutions is excited by femtosecond pulses generated with the use of Ti:Sa laser tuned within the range of 740-790 nm. It is observed that fluorescence lifetime of ICG in water is 0.166 ± 0.02 ns and does not depend on excitation and emission wavelengths. We also show that for the diffusely scattering solvents (milk and intralipid), the lifetime may depend on the dye concentration (especially for large concentrations of ICG). This effect should be taken into account when analyzing changes in the mean time of arrival of fluorescence photons excited in ICG dissolved in such optically turbid media.
Recently, it was shown in measurements carried out on humans that time-resolved near-infrared reflectometry and fluorescence spectroscopy may allow for discrimination of information originating directly from the brain avoiding influence of contaminating signals related to the perfusion of extracerebral tissues. We report on continuation of these studies, showing that the near-infrared light can be detected noninvasively on the surface of the tissue at large interoptode distance. A multichannel time-resolved optical monitoring system was constructed for measurements of diffuse reflectance in optically turbid medium at very large source-detector separation up to 9 cm. The instrument was applied during intravenous injection of indocyanine green and the distributions of times of flight of photons were successfully acquired showing inflow and washout of the dye in the tissue. Time courses of the statistical moments of distributions of times of flight of photons are presented and compared to the results obtained simultaneously at shorter source-detector separations (3, 4, and 5 cm). We show in a series of experiments carried out on physical phantom and healthy volunteers that the time-resolved data acquisition in combination with very large source-detector separation may allow one to improve depth selectivity of perfusion assessment in the brain.
To facilitate the design and optimization of instruments for time-domain optical brain imaging within the European
project "nEUROPt", the performance of various instruments is assessed and compared. This type of instruments relies on
picosecond lasers with high repetition rates, fast detectors and time-correlated single photon counting. The first step of
the assessment included a number of basic tests that are related to parameters of the source, to the differential
nonlinearity of the timing electronics and to the temporal instrument response function (IRF). An additional test has been
devised to measure the responsivity of the detection system, i.e. the overall efficiency to collect and detect light
emerging from tissue. Dedicated solid slab phantoms have been developed and quantitatively spectrally characterized to
provide sources of known radiance with nearly Lambertian angular characteristics. The wavelength-dependent
transmittance factor of these phantoms was of the order of 1020/(W s m2sr). Measurements of the responsivity of the
detection systems of three time-domain optical brain imagers tested yielded similar values of the order of 0.1 mm2sr.
An imaging system for brain oxygenation based on a time-gated, intensified charge-coupled device camera was developed. It allows one to image diffusely reflected light from an investigated medium at defined time windows delayed with respect to the laser pulse. Applying a fast optomechanical switch to deliver the light at a wavelength of 780 nm to nine source fibers allowed one to acquire images in times as short as 4 s. Thus, the system can be applied in in vivo studies. The system was validated in phantom experiments, in which absorbing inclusions were localized at different depths and different lateral positions. Then, the decrease in absorption of the brain tissue related to increase in oxygenation was visualized in the motor cortex area during finger tapping by a healthy volunteer.
A time-resolved optical instrument allowing for noninvasive assessment of cerebral oxygenation is presented. The instrument is equipped with picosecond diode lasers, fast photodetectors, and time-correlated single photon counting electronics. This technology enables depth-resolved estimation of changes in absorption and, in consequence, assessment of changes in hemoglobin concentrations in the brain cortex. Changes in oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) can be evaluated selectively in extra- and intracerebral tissue compartments using the moments of distributions of times of flight of photons measured at two wavelengths in the near-infrared region. The combination of the data acquired from multiple sources and detectors located on the surface of the head with the depth-resolved analysis, based on the moments, enables imaging of cortex oxygenation. Results of the tests on physical phantoms as well as in vivo validation of the instrument during the motor stimulation experiment are presented.
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