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Monitoring of human tissue hemodynamics is invaluable in clinics as the proper blood flow regulates cellular-level metabolism. Time-domain diffuse correlation spectroscopy (TD-DCS) enables noninvasive blood flow measurements by analyzing temporal intensity fluctuations of the scattered light. With time-of-flight (TOF) resolution, TD-DCS should decompose the blood flow at different sample depths. For example, in the human head, it allows us to distinguish blood flows in the scalp, skull, or cortex. However, the tissues are typically polydisperse. So photons with a similar TOF can be scattered from structures that move at different speeds. Here, we introduce a novel approach that takes this problem into account and allows us to quantify the TOF-resolved blood flow of human tissue accurately. We apply this approach to monitor the blood flow index in the human forearm in vivo during the cuff occlusion challenge. We detect depth-dependent reactive hyperemia. Finally, we applied a controllable pressure to the human forehead in vivo to demonstrate that our approach can separate superficial from the deep blood flow. Our results can be beneficial for neuroimaging sensing applications that require short interoptode separation.

The pathophysiology of atherosclerosis and acute coronary syndrome (ACS) is related to interactions between immune cells, endothelium, and blood platelets. An increasing number of reports confirm the link between excessive immune activation and cellular cross-talk with ACS incidence. Our genetic and proteomic analysis was performed on strictly selected atherosclerotic patients with non-fatal ACS without typical risk factors and healthy donors. Results showed changes in the gene expression levels of the various inflammatory factors derived from the peripheral blood cells that drive the over-activation of the immune system. The enhanced activation of the immune system may lead to the overexpression of the pro-inflammatory mediators, which causes self-perpetuating machinery of processes associated with thrombosis. In our preliminary study, we confirmed an altered expression of genes associated with the inflammation and overall interaction of the vascular microenvironment. Furthermore, 5 of 92 analyzed genes, CCL2, CCR2, CSF2, GZMB, and ICOS, were expressed only in patients with ACS. In conclusion, the augmented expression of the pro-inflammatory genes from the peripheral blood cells may be a crucial genetic factor leading to the occurrence of acute inflammation and thus be significant in ACS pathogenesis.

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.

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.

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 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 evaluated the properties of oscillations in the Mayer waves (MW) frequency range ([Formula: see text][Formula: see text]Hz) detected in blood pressure, heart rate variability, cerebral blood oxygenation changes and evolution of electroencephalographic (EEG) rhythms to elucidate the mechanisms of MW generation. We examined the persistence of MW in different signals and stability of their oscillations on the level of individual MW waveforms, which was achieved by applying matching pursuit (MP). MP yields adaptive time-frequency approximation of signal’s structures in terms of frequency, amplitude, time occurrence, and time-span. The number of waveforms contributing to 95% of the energy of the signals was vastly different for the time series, but the average number of waveforms conforming to the MW criteria was almost the same ([Formula: see text] per 120[Formula: see text]s epoch). In all the investigated signals, MW had the same distributions of frequency and the number of cycles. We show that the MW energy ratios in different signals varied strongly, [Formula: see text]. The highest percentage of MW energy was observed in blood pressure signals, heart rate variability, and reduced hemoglobin, in contrast to brain signals and oxygenated hemoglobin. The percentage of MW energy was related to the strength of causal influence exerted by them on the other signals. Our results indicate existence of a common mechanism of MW generation and support the hypothesis of MW generation in the baroreflex loop; however, they do not exclude the action of a central pacemaker.

A multi-laboratory exercise, involving 29 diffuse optical instruments, aimed at performance assessment of diffuse optics instruments on standardized protocols is presented. The overarching methodology and future actions will also be discussed.

A novel technique for imaging of a small animal with application of time-gated intensified CCD camera was proposed. The time-resolved method based on emission of picosecond light pulses and detection of the light penetrating in tissues was applied. In this technique, the fluorescence photons, excited in the dye circulating in the tissue, that diffusely penetrate in the optically turbid medium are detected. The data acquired during measurements carried out on a rat was analyzed in order to estimate fluorescence lifetime which depends strongly on the environment in which the dye is distributed. In the lifetime estimation a special emphasis was put on compensation of influence of the instrumental response function of the setup on the measured quantity. The proposed optical system was validated in series of phantom experiments, in which estimates of fluorescence lifetime of inclusions containing indocyanine green (ICG) were obtained. ICG is a dye revealing florescence properties in near-infrared wavelength region. Images of the estimate of fluorescence lifetime of the ICG accumulated in tissues of a rat were successfully acquired around six circular spots of illumination of the diameter of 6 mm. Larger lifetime values were observed in lung/heart region of the animal. Aspect of sampling rate of the fluorescence lifetime images optimization was finally discussed.

Background: In the era of modern interventional cardiology, implantation of a balloon expandable stent is the finishing touch of almost every coronary angioplasty. However, sometimes we face a clinical situation in which the decision regarding the stent diameter is complicated, especially in the ectatic part of arteries, in situations when the artery lumen is obscured with the thrombus, or when the reference diameter of the proximal and distal part of the lesion vary greatly. That is why the idea of a self-apposing stent similar to the one used in peripheral vascular interventions was adopted into cardiology. Aim: The aim of this study was to present a single-centre registry of STENTYS® stent implantation in 40 selected patients with acute coronary syndromes (ACS) or with stable angina (coronary artery disease [CAD]) treated with this self-expandable stent. Methods and Results: The device was successfully implanted in all patients. During in-hospital observation and 30-day follow-up there were two cases of death, but none of the patients had acute stent thrombosis or ACS ST elevation myocardial infarction. In one case ACS type 4b was diagnosed. In all patients the stent was delivered in the target lesion. In two cases the procedure was performed in patients with multivessel CAD extending into the left main stem in a state of cardiogenic shock. These patients died immediately after the procedure. There were two procedure complications: in one case dissection after post dilatation occurred distally to the stent, and in one patient the calcified proximal part of the left anterior descending artery was dissected with system passage. Thirty-eight patients survived the 12-month follow-up period, and three (7.8%) patients underwent repeated target-lesion revascularisation. Conclusions: In the presented single-centre registry the STENTYS® stent was used with a high delivery and procedural success rate. Satisfactory clinical long-term outcome both in stable patients and ACS patients with a repeated revascularisation ratio of 7.8% was observed. The stent design allowed successful treatment of bifurcation lesions.

In this paper, we propose the application of time-domain near-infrared spectroscopy to the assessment of oscillations in cerebral hemodynamics. These oscillations were observed in the statistical moments of the distributions of time of flight of photons (DTOFs) measured on the head. We analyzed the zeroth and second centralized moments of DTOFs (total number of photons and variance) to obtain their spectra to provide parameters for the frequency components of microcirculation, which differ between the extracerebral and intracerebral layers of the head. Analysis of these moments revealed statistically significant differences between a control group of healthy subjects and a group of patients with severe neurovascular disorders, which is a promising result for the assessment of cerebral microcirculation and cerebral autoregulation mechanisms.

We present an overview of the wide range of potential applications of optical methods for monitoring traumatic brain injury. The MEDLINE database was electronically searched with the following search terms: “traumatic brain injury,” “head injury,” or “head trauma,” and “optical methods,” “NIRS,” “near-infrared spectroscopy,” “cerebral oxygenation,” or “cerebral oximetry.” Original reports concerning human subjects published from January 1980 to June 2015 in English were analyzed. Fifty-four studies met our inclusion criteria. Optical methods have been tested for detection of intracranial lesions, monitoring brain oxygenation, assessment of brain perfusion, and evaluation of cerebral autoregulation or intracellular metabolic processes in the brain. Some studies have also examined the applicability of optical methods during the recovery phase of traumatic brain injury . The limitations of currently available optical methods and promising directions of future development are described in this review. Considering the outstanding technical challenges, the limited number of patients studied, and the mixed results and opinions gathered from other reviews on this subject, we believe that optical methods must remain primarily research tools for the present. More studies are needed to gain confidence in the use of these techniques for neuromonitoring of traumatic brain injury patients.

A methodology for the assessment of the cerebral hemodynamic reaction to normotensive hypovolemia, reduction in cerebral perfusion and orthostatic stress leading to ischemic hypoxia and reduced muscular tension is presented. Most frequently, the pilots of highly maneuverable aircraft are exposed to these phenomena. Studies were carried out using the system consisting of a chamber that generates low pressure around the lower part of the body - LBNP (lower body negative pressure) placed on the tilt table. An in-house developed 6-channel NIRS system operating at 735 and 850 nm was used in order to assess the oxygenation of the cerebral cortex, based on measurements of diffusely reflected light in reflectance geometry. The measurements were carried out on a group of 12 active pilots and cadets of the Polish Air Force Academy and 12 healthy volunteers. The dynamics of changes in cerebral oxygenation was evaluated as a response to LBNP stimuli with a simultaneous rapid change of the tilt table angle. Parameters based on calculated changes of total hemoglobin concentration were proposed allowing to evaluate differences in reactions observed in control subjects and pilots/cadets. The results of orthogonal partial least squares-discriminant analysis based on these parameters show that the subjects can be classified into their groups with 100% accuracy.

The aim of the study was to assess causal coupling between neuronal activity, microvascular hemodynamics and blood supply oscillations in the Mayer wave frequency range. An electroencephalogram, cerebral blood oxygenation changes, an electrocardiogram and blood pressure were recorded during rest and during a movement task. Causal coupling between them was evaluated using directed transfer function, a measure based on the Granger causality principle. The multivariate autoregressive model was fitted to all the signals simultaneously, which made it possible to construct a complete scheme of interactions between the considered signals. The obtained pattern of interactions in the resting state estimated in the 0.05–0.15 Hz band revealed a predominant influence of blood pressure oscillations on all the other variables. Reciprocal connections between blood pressure and heart rate variability time series indicated the presence of feedback loops between these signals. During movement, the pattern of connections did not change dramatically. The number of connections decreased, but the couplings between blood pressure and heart rate variability signal were not significantly changed, and the strong influence of the decreased blood hemoglobin concentration on the oxygenated hemoglobin concentration persisted. For the first time our results provided a comprehensive scheme of interactions between electrical and hemodynamic brain signals, heart rate and blood pressure oscillations. Persistent reciprocal connections between blood pressure and heart rate variability time series suggest possible feedforward and feedback coupling of cardiovascular variables which may lead to the observed oscillations in Mayer wave range.

An optical technique based on diffuse reflectance measurement combined with indocyanine green (ICG) bolus tracking is extensively tested as a method for the clinical assessment of brain perfusion at the bedside. We report on multiwavelength time-resolved diffuse reflectance spectroscopy measurements carried out on the head of a healthy adult during the intravenous administration of a bolus of ICG. Intracerebral and extracerebral changes in absorption were estimated from an analysis of changes in statistical moments (total number of photons, mean time of flight and variance) of the distributions of times of flight (DTOF) of photons recorded simultaneously at 16 wavelengths from the range of 650–850 nm using sensitivity factors estimated by diffusion approximation based on a layered model of the studied medium. We validated the proposed method in a series of phantom experiments and in-vivo measurements. The results obtained show that changes in the concentration of the ICG can be assessed as a function of time of the experiment and depth in the tissue. Thus, the separation of changes in ICG concentration appearing in intra- and extracerebral tissues can be estimated from optical data acquired at a single source-detector pair of fibers/fiber bundles positioned on the surface of the head.

Cerebral blood flow and hemoglobin concentration measured by diffuse correlation spectroscopy and time-resolved spectroscopy in patients with traumatic brain injury show different behaviour during hyperventilation therapy according to the functioning of the treatment.

Transcranial direct current stimulation (tDCS) is currently being used for research and treatment of some neurological and neuropsychiatric disorders, as well as for improvement of cognitive functions. In order to better understand cerebral response to the stimulation and to redefine protocols and dosage, its effects must be monitored. To this end, we have used functional diffuse correlation spectroscopy (fDCS) and time-resolved functional near-infrared spectroscopy (TR-fNIRS) together with electroencephalography (EEG) during and after stimulation of the frontal cortex. Twenty subjects participated in two sessions of stimulation with two different polarity montages and twelve also underwent a sham session. Cerebral blood flow and oxyhemoglobin concentration increased during and after active stimulation in the region under the stimulation electrode while deoxyhemoglobin concentration decreased. The EEG spectrum displayed statistically significant power changes across different stimulation sessions in delta (2 to 4 Hz), theta (4 to 8 Hz), and beta (12 to 18 Hz) bands. Results suggest that fDCS and TR-fNIRS can be employed as neuromonitors of the effects of transcranial electrical stimulation and can be used together with EEG.

Due to increased life expectancy and unfavorable cardiovascular risk profile in persons with haemophilia (PWH), physicians may face the problem of using potentially contraindicated antiplatelet drugs in this vulnerable to bleedings group of patients. Current European guidelines recommend usage of dual antiplatelet therapy (DAPT) for 12 months after acute coronary syndrome (ACS), whereas haemophilia specialists suggest that such aggressive treatment should be limited to a minimum. The aim of our case report was to assess whether ticagrelor could be a component of DAPT in PWH presenting ACS. We present the case of 67-years-old male with severe haemophilia A and ST-segment elevation myocardial infarction, who required percutaneous coronary intervention with implantation of 5 drug-eluting stents (DES). Due to high risk of stent thrombosis, after thorough discussion with hematologist, we decided to treat the patient with ticagrelor, acetylsalicylic acid and prophylactic doses of factor VIII. Recommended treatment was well tolerated, without angina and bleeding episodes during follow-up. In our opinion usage of DES and extended DAPT with ticagrelor may be considered in PWH and ACS with elevated risk of restenosis. Concomitant prophylactic doses of clotting factors should ensure the safety of the treatment used as in the general population.

We aimed to determine whether optical methods based on bolus tracking of an optical contrast agent are useful for the confirmation of cerebral circulation cessation in patients being evaluated for brain death. Different stages of cerebral perfusion disturbance were compared in three groups of subjects: controls, patients with posttraumatic cerebral edema, and patients with brain death. We used a time-resolved near-infrared spectroscopy setup and indocyanine green (ICG) as an intravascular flow tracer. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was carried out to build statistical models allowing for group separation. Thirty of 37 subjects (81.1%) were classified correctly (8 of 9 control subjects, 88.9%; 13 of 15 patients with edema, 86.7%; and 9 of 13 patients with brain death, 69.2%; p

The aim of this study was to verify the usefulness of the time-resolved optical method utilizing diffusely reflected photons and fluorescence signals combined with intravenous injection of indocyanine green (ICG) in the assessment of brain perfusion in post-traumatic brain injury patients. The distributions of times of flight (DTOFs) of diffusely reflected photons were acquired together with the distributions of times of arrival (DTAs) of fluorescence photons. The data analysis methodology was based on the observation of delays between the signals of statistical moments (number of photons, mean time of flight and variance) of DTOFs and DTAs related to the inflow of ICG to the extra- and intracerebral tissue compartments. Eleven patients with brain hematoma, 15 patients with brain edema and a group of 9 healthy subjects were included in this study. Statistically significant differences between parameters obtained in healthy subjects and patients with brain hematoma and brain edema were observed. The best optical parameter to differentiate patients and control group was variance of the DTOFs or DTAs. Results of the study suggest that time-resolved optical monitoring of inflow of the ICG seems to be a promising tool for detecting cerebral perfusion insufficiencies in critically ill patients.

An intra-abdominal pressure (IAP) is correlated with cerebral perfusion, in a mechanism of reducing venous outflow. The elevated intra-abdominal pressure leads to an increase in the intracranial pressure and a decrease in the cerebral perfusion pressure. We studied the relationship between the IAP and the cerebral oxygenation with the use of the near infrared spectroscopy technique during a gynecological surgery. The changes in hemoglobin concentrations were analyzed in the time-frequency domain in the frequency band related to respiration. The measurements were carried out in 15 subjects who underwent laparoscopic surgery. During the laparoscopy, the intra-abdominal cavity was insufflated with CO(2), which caused a controlled increase in the IAP. It was observed that the amplitudes of respiration-related waves present in hemoglobin concentration signals show an increase of 1.5 to 8.5 times during elevation of the IAP by 15 mmHg.

We have developed a high-resolution diffuse optical tomography system capable of carrying out measurements on an adult human head at source-detector separations 1.5-11.8cm. We present first results obtained during a Valsalva maneuver.

A time-gated intensified CCD camera was applied for time-resolved imaging of light penetrating in an optically turbid medium. Spatial distributions of light penetration probability in the plane perpendicular to the axes of the source and the detector were determined at different source positions. Furthermore, visiting probability profiles of diffuse reflectance measurement were obtained by the convolution of the light penetration distributions recorded at different source positions. Experiments were carried out on homogeneous phantoms, more realistic two-layered tissue phantoms based on the human skull filled with Intralipid-ink solution and on cadavers. It was noted that the photons visiting probability profiles depend strongly on the source-detector separation, the delay between the laser pulse and the photons collection window and the complex tissue composition of the human head.

It was reported that time-resolved reflectance measurements carried out during inflow and washout of an optical contrast agent may provide information on the blood supply to the brain cortex of human adults. It was also shown that a measurement of fluorescence excited in the dye circulating in the brain is feasible. Unfortunately, patterns of time-resolved fluorescence signals observed during in vivo measurements are difficult to interpret. The aim of this study was to analyze the influence of several factors on the fluorescence signals measured during in vivo experiments. A laboratory instrument for recording the distributions of arrival of fluorescence photons was constructed and optimized for measurements on humans. Monte Carlo simulations and laboratory measurements on liquid phantoms as well as in vivo measurements on healthy volunteers were carried out. An influence of source-detector separation, position of the source-detector pair on the head, as well as a dose of the injected indocyanine green (ICG) on the fluorescence signals were studied in detail. It was shown that even for a small dose of ICG (0.025 mg kg(-1)) the time-resolved signals can be successfully detected on the surface of the head. Strong influence of the studied factors on the fluorescence signals was observed. It was also noted that the changes in moments of distributions of arrival times of fluorescence photons depend on the anatomical structure of the tissues located between the source and the detector.

The in-vivo optical properties of the human head are investigated in the 600-1100 nm range on different subjects using continuous wave and time domain diffuse optical spectroscopy. The work was performed in collaboration with different research groups and the different techniques were applied to the same subject. Data analysis was carried out using homogeneous and layered models and final results were also confirmed by Monte Carlo simulations. The depth sensitivity of each technique was investigated and related to the probed region of the cerebral tissue. This work, based on different validated instruments, is a contribution to fill the existing gap between the present knowledge and the actual in-vivo values of the head optical properties. (C) 2015 Optical Society of America

Dynamic mapping of the human brain by time-resolved near-infrared-spectroscopy (trNIRS), or functional NIRS (fNIRS), is based on the injection of picosecond or sub-nanosecond laser pulses into the head and the measurement of the pulse shape and the intensity after diffusion through the tissue. By analysing the pulse shape and the intensity of the signals at different detector and source positions and different wavelengths, changes in the oxy- and deoxy-haemoglobin concentration are obtained for extracerebral and intracerebral tissue layers and for different depth in the brain. The technique can by combined with the injection of a bolus of an exogenous absorber. By recording either absorption or fluorescence, the in- and outflow of the absorber in different brain compartments can be monitored. The in- and outflow dynamics reveal differences in the blood flow caused by impaired perfusion or stroke. In this chapter, we describe the technical principle of TCSPC-based fNIRS and the associated data processing techniques. Typical results are shown for the haemodynamic response of the brain on visual-cortex stimulation, and for brain perfusion measurement by ICG bolus injection.

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. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.

A multi-center study has been set up to accurately characterize the optical properties of diffusive liquid phantoms based on Intralipid and India ink at near-infrared (NIR) wavelengths. Nine research laboratories from six countries adopting different measurement techniques, instrumental set-ups, and data analysis methods determined at their best the optical properties and relative uncertainties of diffusive dilutions prepared with common samples of the two compounds. By exploiting a suitable statistical model, comprehensive reference values at three NIR wavelengths for the intrinsic absorption coefficient of India ink and the intrinsic reduced scattering coefficient of Intralipid-20% were determined with an uncertainty of about 2% or better, depending on the wavelength considered, and 1%, respectively. Even if in this study we focused on particular batches of India ink and Intralipid, the reference values determined here represent a solid and useful starting point for preparing diffusive liquid phantoms with accurately defined optical properties. Furthermore, due to the ready availability, low cost, long-term stability and batch-to-batch reproducibility of these compounds, they provide a unique fundamental tool for the calibration and performance assessment of diffuse optical spectroscopy instrumentation intended to be used in laboratory or clinical environment. Finally, the collaborative work presented here demonstrates that the accuracy level attained in this work for optical properties of diffusive phantoms is reliable. © 2014 Optical Society of America.

Time-resolved, fluorescence tomography system for small animals imaging was constructed. The setup is based on time-gated intensified CCD camera and picosecond laser. Preliminary experiments on rat-phantom with fluorescent inclusions were carried out

Time-resolved fluorescence measurements were carried out on the head during indocyanine green (ICG) injection. The ICG washout rate was estimated in patients with severe cerebral perfusion abnormalities: brain edema, blood-brain barrier disruption and brain death.

The optical properties of the human head in the range from 600 nm to 1100 nm have been non-invasively investigated by various research groups using different diffuse optics techniques and data analysis methods.

Time-resolved near-infrared spectroscopy is an optical technique which can be applied in tissue oxygenation assessment. In the last decade this method is extensively tested as a potential clinical tool for noninvasive human brain function monitoring and imaging. In the present paper we show construction of an instrument which allows for: (i) estimation of changes in brain tissue oxygenation using two-wavelength spectroscopy approach and (ii) brain perfusion assessment with the use of single-wavelength reflectometry or fluorescence measurements combined with ICG-bolus tracking. A signal processing algorithm based on statistical moments of measured distributions of times of flight of photons is implemented. This data analysis method allows for separation of signals originating from extra- and intracerebral tissue compartments. In this paper we present compact and easily reconfigurable system which can be applied in different types of time-resolved experiments: two-wavelength measurements at 687 and 832 nm, single wavelength reflectance measurements at 760 nm (which is at maximum of ICG absorption spectrum) or fluorescence measurements with excitation at 760 nm. Details of the instrument construction and results of its technical tests are shown. Furthermore, results of in-vivo measurements obtained for various modes of operation of the system are presented.

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.

Measurements of optical translucency of human skulls were carried out. An incandescent light source and a CCD camera were used to measure the distribution of light transmitted through the skull in 10 subjects post-mortem. We noticed that intra-individual differences in optical translucency may be up to 100 times but inter-individual translucency differences across the skull reach 105 times. Based on the measurement results, a “theoretical” experiment was simulated. Monte-Carlo calculations were used in order to evaluate the influence of the differences in optical translucency of the skull on results of NIRS measurements. In these calculations a functional stimulation was done, in which the oxyhemoglobin and deoxyhemoglobin concentrations in the brain cortex change by 5μM and −5μM respectively. The maximal discrepancies between assumed hemoglobin concentration changes and hemoglobin concentration changes estimated with Monte-Carlo simulation may reach 50% depending of the translucency of the skull.

The near infrared spectroscopy may be implemented using various optoelectronic techniques, however, most of them do not allow to carry out measurements at short source-detector separation. We propose a method, based on time-gated intensified CCD camera, which allows for contactless measurements and can be carried out at short source-detector separation. This technique was tested on a phantom with absorbing inclusions buried in an optically turbid medium which mimics local changes in oxygenation of the brain tissue.

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.

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.