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.
Time domain diffuse correlation spectroscopy (td-DCS), has been proposed as a method that can increase the sensitivity of DCS for detecting blood flow index (BFI) in deep tissue. Several important parameters including the instrument response function (IRF), gate start time, gate width, and source-detector separation (SDS) must be taken into consideration. In our study, we characterized td-DCS system at three different SDS values and assessed each SDS's ability to detect dynamic changes of blood flow caused by moving red blood cells during cuff occlusion.
This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions.
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.
Hybrid device for the study of blood flow index and hemoglobins concentrations changes was developed. Diffuse correlation spectroscopy and time-resolved near-infrared spectroscopy were applied to study brain hemodynamics of healthy adults human during the Valsalva maneuver.
We show the hemodynamic response of a visual cortex on healthy volunteers under, hypoxia as registered with fNIRS system. Results show that amplitude of hemodynamic response to a visual stimulation correlates with the arterial oxygen saturation.
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.
KEYWORDS: Visualization, Linear filtering, In vivo imaging, Signal detection, Sensors, Homodyne detection, Brain, Tissues, Hemodynamics, Electronic filtering
We introduce method of lock-in amplifying optical signals originating within brain. It requires 90-degree rotated source-detector pairs. In-vivo results suggest the proposed hardware and algorithm are brain-sensitive and real-time.
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.
Time-domain fNIRS facilitates the elimination of the influence of extracerebral, systemic effects on measured signals since it contains time-of-flight information that is related to the penetration depth. Employing perturbation and MonteCarlo simulations, we quantitatively characterized and compared the performance of measurands based on moments and time windows of time-of-flight distributions. We extend our analysis to investigate whether higher moments and MellinLaplace (ML) moments promise improvements in performance. The comparison is based on spatial sensitivity profiles as well as metrics for relative contrast, contrast-to-noise ratio (CNR), depth selectivity, and the product of CNR and depth selectivity for layered absorption changes. The influence of reduced scattering coefficient, thickness of the superficial layer, and source-detector distance was analyzed. The third central moment performs similarly to variance and is worth considering for data analyzes. Higher order ML moments perform similarly to time windows and they likewise provide variable depth selectivity.
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.
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.
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.
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.
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.
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 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.
KEYWORDS: Optical properties, Monte Carlo methods, Data modeling, Tissue optics, Medical research, Statistical analysis, Absorption, Scattering, Tissues, Error analysis
The analysis of statistical moments of time-resolved (TR) diffuse optical signals can be used to evaluate the absorption and scattering coefficients of turbid media; however, this method requires careful measurement of the instrument response function. We propose an alternative approach that avoids this step by estimating the optical properties from the difference of TR measurements acquired at different source-detector separations. The efficiency of this method was validated using simulated data (from analytical model and Monte-Carlo simulations) and tissue-mimicking phantoms. Results for a homogenous and layered medium showed that the subtraction technique can accurately estimate the optical properties. Specifically, our preliminary results show that the method can estimate the optical properties of a homogeneous medium (simulated using μa = 0.1 mm-1, μs’ = 10 mm-1) with an error less than 10 %. Accurate results were obtained at source-detector separations large enough (5 mm or greater) to resolve differences in the moments. Moreover, we also observed that the subtraction method has improved depth sensitivity compared to the classic method of moments. These results suggests that time-resolved subtraction is a simple but effective means of quantifying optical properties of turbid media, in addition to offering a new approach for obtaining spatially sensitive measurements, although additional studies are required to confirm the latter.
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.
Optical technique based on diffuse reflectance measurement combined with indocyanine green (ICG) bolus tracking is extensively tested as a method for clinical assessment of brain perfusion in adults at the bedside. Methodology of multiwavelength and time-resolved detection of fluorescence light excited in the ICG is presented and advantages of measurements at multiple wavelengths are discussed. Measurements were carried out: 1. on a physical homogeneous phantom to study the concentration dependence of the fluorescence signal, 2. on the phantom to simulate the dynamic inflow of ICG at different depths, and 3. in vivo on surface of the human head. Pattern of inflow and washout of ICG in the head of healthy volunteers after intravenous injection of the dye was observed for the first time with time-resolved instrumentation at multiple emission wavelengths. The multiwavelength detection of fluorescence signal confirms that at longer emission wavelengths, probability of reabsorption of the fluorescence light by the dye itself is reduced. Considering different light penetration depths at different wavelengths, and the pronounced reabsorption at longer wavelengths, the time-resolved multiwavelength technique may be useful in signal decomposition, leading to evaluation of extra- and intracerebral components of the measured signals.
Time-resolved near-infrared spectroscopy allows for depth-selective determination of absorption changes in the adult human head that facilitates separation between cerebral and extra-cerebral responses to brain activation. The aim of the present work is to analyze which combinations of moments of measured distributions of times of flight (DTOF) of photons and source-detector separations are optimal for the reconstruction of absorption changes in a two-layered tissue model corresponding to extra- and intra-cerebral compartments. To this end we calculated the standard deviations of the derived absorption changes in both layers by considering photon noise and a linear relation between the absorption changes and the DTOF moments. The results show that the standard deviation of the absorption change in the deeper (superficial) layer increases (decreases) with the thickness of the superficial layer. It is confirmed that for the deeper layer the use of higher moments, in particular the variance of the DTOF, leads to an improvement. For example, when measurements at four different source-detector separations between 8 and 35 mm are available and a realistic thickness of the upper layer of 12 mm is assumed, the inclusion of the change in mean time of flight, in addition to the change in attenuation, leads to a reduction of the standard deviation of the absorption change in the deeper tissue layer by a factor of 2.5. A reduction by another 4% can be achieved by additionally including the change in variance.
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.
We present a multi-laboratory comparison of several independent forward solvers used for photon migration
through layered media. Two main categories of forward solvers are presented: Monte Carlo procedures and
solutions of the diffusion equation for the time domain. For Monte Carlo we have included four independent
codes. For the solutions of the diffusion equation, we have presented: two semi-analytical approaches based
on the Green's function method and one solution obtained with the finite element method. The comparisons
between the different time-dependent solutions were performed for a two-layer medium.
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.
We present a multi-dimensional TCSPC technique that simultaneously records the photon distribution over the time in the
fluorescence decay, the wavelength, and the coordinates of a two-dimensional scan or the time since the start of the experiment.
We demonstrate the application of the technique to diffuse optical tomography, single-point autofluorescence measurements
of skin, and multi-spectra autofluorescence lifetime imaging of tissue.
Optical techniques based on photon migration are rapidly emerging as a promising alternative and/or augmentation of existing medical imaging modalities. For example, real time studies of hemodynamic changes in brain tissue are possible as a step towards optical functional brain imaging. Time-resolved implementations of these techniques allow for discrimination between scattering and absorption and for depth resolution. They require sub-nanosecond pulsed light sources with high repetition rate and sufficient power for deep enough tissue penetration. Picosecond diode lasers satisfy the clinical demands of economy, compact size, and reliability almost perfectly. Today multi-channel diode laser devices are commercially available and are widely used in diffuse optical imaging and spectroscopy, in particular in optical tomography and breast cancer detection. However, the output powers of these devices are just about sufficient for moderate tissue penetration depths. An improvement that does not compromise the advantages of the diode laser sources is amplification of the diode laser output by means of solid state tapered amplifiers. We present an amplified light source for use in NIR diffuse optical spectroscopy and imaging, providing pulse widths as short as 100 ps, adjustable repetition rates up to 80 MHz, and peak power levels as high as 7 Watts, corresponding to average power levels exceeding 100 mW. In combination with time-resolved photon counting electronics matching the high throughput demands in conjunction with the new source, state-of-the-art systems for diffuse optical imaging can be built. System design features and possible application examples are presented.
Time-resolved optical measurements allow for evaluation of optical properties of the tissue (in particular, absorption and reduced scattering coefficient). A four-channel time-resolved spectroscopic system for measurements of the tissue optical properties is presented. Four semiconductor diode lasers were used for emission of picosecond pulses at wavelengths of 633, 687, 784 and 832 nm. Optical fibers were applied to deliver the laser light into the tissue studied. The diffusely reflected light was transmitted to the photodetectors through fiber bundles. Four photomultiplier tubes were used for light detection and four independent time-correlated single photon counting boards were applied to obtain distributions of times of flight of photons. Measurements on liquid phantoms were carried out to test the temporal resolution and stability of the system and to demonstrate its usefulness in non-invasive determination of optical properties of the tissue.
NIRS signals measured on the adult head contain contributions from the brain and from overlying tissue. It was shown recently that measured distributions of times of flight (DTOF) of photons allow to deduce absorption changes occurring in different layers of the head. This method relies on time-dependent mean partial pathlengths calculated by Monte Carlo simulations for assumed background optical properties of the various tissues. Deconvolution of the measured
DTOF is required using the instrumental response function. We propose an alternative method to estimate absorption changes in various tissue layers by analyzing changes of moments of DTOFs (integral, mean time of flight and variance) recorded at various source-detector separations. The sensitivity factors corresponding to integral, mean time of flight and variance were obtained by Monte Carlo simulations for a layered model of the head. From experimentally derived mean time of flight and variance the contributions of the instrumental response function were subtracted. The proposed method was applied to multi-distance time-domain measurements during functional stimulation of the brain of healthy volunteers.
Two time-domain scanning optical mammographs are presently tested in clinical trials within the EU project "OPTIMAMM" supported by the EC. To assess their performance (e.g., accuracy, sensitivity, stability), systematic measurements were performed on breast-like phantoms. Both, estimation of optical properties and acquisition of good contrast images for diagnostic purposes were considered. The proposed
assessment procedure can be applied to characterize and improve other novel and existing instruments for photon migration imaging and spectroscopy.
We present a newly developed scanning time-resolved optical mammograph for breast cancer detection featuring four wavelengths for enhanced spectroscopic information, up to 6 off-axis detection channels for improved depth localisation and novel attenuation and imaging optics for improved response reproducibility and photon collection efficiency. First results on the characterisation and on performance tests of this mammograph are shown.
The Laser-Doppler (LD) method is extensively used in clinical experiments for microcirculation measurement. The results of LD perfusion measurements depends on technical factors such as laser light wavelength, LD probe arrangement, and signal processing algorithm. The aim of this study is to compare the output of various signal processing algorithms (LDP) with the use of digital spectral analysis of the photodetector current. Comparison is made with the output of a commercial LD instrument (LDF). The results obtained using a simple one-tube physical model confirm that the best linearity of response of the LD instrument for changes of flow velocity is given by the algorithm based on first moment of power spectral density of AC component of photodetector's signal.
This paper reviews the development and use of laser Doppler perfusion monitors and imagers. Despite their great success and almost universal applicability in microcirculation research, they have had great difficulty in converting to widespread clinical application. The enormous interest in microvascular blood perfusion coupled with the 'ease of use' of the technique has led to 2000+ publications citing its use. However, useful results can only be achieved with an understanding of the basic principles of the instrumentation and its application in the various clinical disciplines. The basic technical background is explored and definitions of blood perfusion and laser Doppler perfusion are established. The calibration method is then described together with potential routes to standardisation. A guide to the limitations in application of the technique gives the user a clear indication of what can be achieved in new studies as well as possible inadequacy in some published investigations. Finally some clinical applications have found acceptability and these will be explored.
An improved Time-Correlated Single Photon Counting (TCSPC) technique features high count rate, low differential nonlinearity and multi-detector capability. The system has four completely parallel TCSPC channels and achieves an effective overall count rate of 20 MHz. By an active routing technique, up to eight detectors can be connected to each of the TCSPC channels. We used the system to record optical mammograms after pulsed laser illumination at different wavelengths and projection angles.
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