Spatially-enhanced time-domain NIRS for accurate determination of tissue optical properties.

A multivariate method integrating time and space resolved techniques of near-infrared spectroscopy is proposed for simultaneously retrieving the absolute quantities of optical absorption and scattering properties in tissues. The time-domain feature of photon migration is advantageously constrained and regularized by its spatially-resolved amplitude patterns in the inverse procedure. Measurements of tissue-mimicking phantoms with various optical properties are analyzed with Monte-Carlo simulations to validate the method performance. The uniqueness, stability, and uncertainty of the method are discussed.

In Vitro Comparisons of Near-Infrared Spectroscopy Oximeters: Impact of Slow Changes in Scattering of Liquid Phantoms.

Several cerebral oximeters based on near-infrared spectroscopy (NIRS) are commercially available that determine tissue oxygen saturation (StO2). One problem is an inconsistency of StO2 readings between different brands of instruments. Liquid blood phantoms mimicking optical properties of the neonatal head enable quantitative device comparisons. However, occasionally, the reduced scattering coefficient (µs') of these phantoms decreases over time. AIM: To investigate whether this decrease in µs' affects the validity of comparison of these devices. StO2 was measured by several NIRS oximeters simultaneously on a phantom, which exhibited a particularly strong decrease in µs'. We found that a decrease in µs' by ≤16% from baseline led to deviations in StO2 of ≤3%.

Forward solvers for photon migration in the presence of highly and totally absorbing objects embedded inside diffusive media.

In this paper, after a critical review of the literature, we present two forward solvers and a new methodology for description of photon migration in the presence of totally absorbing inclusions embedded in diffusive media in both time and CW domains. The first forward solver is a heuristic approach based on a higher order perturbation theory applied to the diffusion equation (DE) [denoted eighth-order perturbation theory (EOPT)]. The second forward solver [denoted eighth-order perturbation theory with the equivalence relation (EOPTER) ] is obtained by combining the EOPT solver with the adoption of the equivalence relation (ER) [J. Biomed. Opt.18, 066014 (2013)]. These forward solvers can possibly overcome some evident limitations of previous approaches like the theory behind the so-called banana-shape regions or exact analytical solutions of the DE in the presence of highly or totally absorbing inclusions. We also propose the ER to reformulate the problem of a totally absorbing inclusion in terms of another inclusion having a finite absorption contrast and a re-scaled volume. For instance, we have shown how this approach can indeed be used to simulate black inclusions with the Born approximation. By means of comparisons with the results of Monte Carlo simulations, we have shown that the EOPTER solver can model totally absorbing inclusions with an error smaller than about 10%, whereas the EOPT solver shows an error smaller than about 20%, showing a performance largely better than that observed with solvers proposed previously.

AAPM Task Group Report 311: Guidance for performance evaluation of fluorescence-guided surgery systems.

The last decade has seen a large growth in fluorescence-guided surgery (FGS) imaging and interventions. With the increasing number of clinical specialties implementing FGS, the range of systems with radically different physical designs, image processing approaches, and performance requirements is expanding. This variety of systems makes it nearly impossible to specify uniform performance goals, yet at the same time, utilization of different devices in new clinical procedures and trials indicates some need for common knowledge bases and a quality assessment paradigm to ensure that effective translation and use occurs. It is feasible to identify key fundamental image quality characteristics and corresponding objective test methods that should be determined such that there are consistent conventions across a variety of FGS devices. This report outlines test methods, tissue simulating phantoms and suggested guidelines, as well as personnel needs and professional knowledge bases that can be established. This report frames the issues with guidance and feedback from related societies and agencies having vested interest in the outcome, coming from an independent scientific group formed from academics and international federal agencies for the establishment of these professional guidelines.

Two-layered blood-lipid phantom and method to determine absorption and oxygenation employing changes in moments of DTOFs.

Near-infrared spectroscopy (NIRS) is an established technique for measuring tissue oxygen saturation (StO2), which is of high clinical value. For tissues that have layered structures, it is challenging but clinically relevant to obtain StO2 of the different layers, e.g. brain and scalp. For this aim, we present a new method of data analysis for time-domain NIRS (TD-NIRS) and a new two-layered blood-lipid phantom. The new analysis method enables accurate determination of even large changes of the absorption coefficient (Δµa) in multiple layers. By adding Δµa to the baseline µa, this method provides absolute µa and hence StO2 in multiple layers. The method utilizes (i) changes in statistical moments of the distributions of times of flight of photons (DTOFs), (ii) an analytical solution of the diffusion equation for an N-layered medium, (iii) and the Levenberg-Marquardt algorithm (LMA) to determine Δµa in multiple layers from the changes in moments. The method is suitable for NIRS tissue oximetry (relying on µa) as well as functional NIRS (fNIRS) applications (relying on Δµa). Experiments were conducted on a new phantom, which enabled us to simulate dynamic StO2 changes in two layers for the first time. Two separate compartments, which mimic superficial and deep layers, hold blood-lipid mixtures that can be deoxygenated (using yeast) and oxygenated (by bubbling oxygen) independently. Simultaneous NIRS measurements can be performed on the two-layered medium (variable superficial layer thickness, L), the deep (homogeneous), and/or the superficial (homogeneous). In two experiments involving ink, we increased the nominal µa in one of two compartments from 0.05 to 0.25 cm-1, L set to 14.5 mm. In three experiments involving blood (L set to 12, 15, or 17 mm), we used a protocol consisting of six deoxygenation cycles. A state-of-the-art multi-wavelength TD-NIRS system measured simultaneously on the two-layered medium, as well as on the deep compartment for a reference. The new method accurately determined µa (and hence StO2) in both compartments. The method is a significant progress in overcoming the contamination from the superficial layer, which is beneficial for NIRS and fNIRS applications, and may improve the determination of StO2 in the brain from measurements on the head. The advanced phantom may assist in the ongoing effort towards more realistic standardized performance tests in NIRS tissue oximetry. Data and MATLAB codes used in this study were made publicly available.

The physiological origin of task-evoked systemic artefacts in functional near infrared spectroscopy.

A major methodological challenge of functional near-infrared spectroscopy (fNIRS) is its high sensitivity to haemodynamic fluctuations in the scalp. Superficial fluctuations contribute on the one hand to the physiological noise of fNIRS, impairing the signal-to-noise ratio, and may on the other hand be erroneously attributed to cerebral changes, leading to false positives in fNIRS experiments. Here we explore the localisation, time course and physiological origin of task-evoked superficial signals in fNIRS and present a method to separate them from cortical signals. We used complementary fNIRS, fMRI, MR-angiography and peripheral physiological measurements (blood pressure, heart rate, skin conductance and skin blood flow) to study activation in the frontal lobe during a continuous performance task. The General Linear Model (GLM) was applied to analyse the fNIRS data, which included an additional predictor to account for systemic changes in the skin. We found that skin blood volume strongly depends on the cognitive state and that sources of task-evoked systemic signals in fNIRS are co-localized with veins draining the scalp. Task-evoked superficial artefacts were mainly observed in concentration changes of oxygenated haemoglobin and could be effectively separated from cerebral signals by GLM analysis. Based on temporal correlation of fNIRS and fMRI signals with peripheral physiological measurements we conclude that the physiological origin of the systemic artefact is a task-evoked sympathetic arterial vasoconstriction followed by a decrease in venous volume. Since changes in sympathetic outflow accompany almost any cognitive and emotional process, we expect scalp vessel artefacts to be present in a wide range of fNIRS settings used in neurocognitive research. Therefore a careful separation of fNIRS signals originating from activated brain and from scalp is a necessary precondition for unbiased fNIRS brain activation maps.

Special Section Guest Editorial: Tissue Phantoms to Advance Biomedical Optical Systems.

The editorial introduces the JBO Special Section on Tissue Phantoms to Advance Biomedical Optical Systems.

Criteria for the design of tissue-mimicking phantoms for the standardization of biophotonic instrumentation.

A lack of accepted standards and standardized phantoms suitable for the technical validation of biophotonic instrumentation hinders the reliability and reproducibility of its experimental outputs. In this Perspective, we discuss general criteria for the design of tissue-mimicking biophotonic phantoms, and use these criteria and state-of-the-art developments to critically review the literature on phantom materials and on the fabrication of phantoms. By focusing on representative examples of standardization in diffuse optical imaging and spectroscopy, fluorescence-guided surgery and photoacoustic imaging, we identify unmet needs in the development of phantoms and a set of criteria (leveraging characterization, collaboration, communication and commitment) for the standardization of biophotonic instrumentation.

Best practices for fNIRS publications.

The application of functional near-infrared spectroscopy (fNIRS) in the neurosciences has been expanding over the last 40 years. Today, it is addressing a wide range of applications within different populations and utilizes a great variety of experimental paradigms. With the rapid growth and the diversification of research methods, some inconsistencies are appearing in the way in which methods are presented, which can make the interpretation and replication of studies unnecessarily challenging. The Society for Functional Near-Infrared Spectroscopy has thus been motivated to organize a representative (but not exhaustive) group of leaders in the field to build a consensus on the best practices for describing the methods utilized in fNIRS studies. Our paper has been designed to provide guidelines to help enhance the reliability, repeatability, and traceability of reported fNIRS studies and encourage best practices throughout the community. A checklist is provided to guide authors in the preparation of their manuscripts and to assist reviewers when evaluating fNIRS papers.

Errata: Best practices for fNIRS publications.

[This corrects the article DOI: 10.1117/1.NPh.8.1.012101.].

Time-resolved near-infrared spectroscopy and imaging of the adult human brain.

Near-infrared spectroscopy (NIRS) of the human brain is aiming at the non-invasive determination of concentration changes of oxy- and deoxyhemoglobin in the cortex. However, it usually relies on the assumption of spatially homogeneous absorption changes. To overcome this limitation we performed instrumental and methodological developments of time-resolved NIRS with the aim to achieve depth resolution. We present our recently developed time-domain near-infrared brain imager based on picosecond diode lasers and time-correlated single photon counting (TCSPC) which can be used at the bedside. To achieve depth localization of absorption changes we analysed statistical moments (integral, mean time of flight and variance) of measured time-of-flight distributions of diffusely reflected photons. In particular, variance has a selective sensitivity to deep absorptions changes and provides a suitable representation of cerebral signals. The separation of cerebral and extracerebral changes of hemoglobin concentrations is demonstrated for a motor stimulation experiment.

Depth-selective data analysis for time-domain fNIRS: moments vs. time windows.

Time-domain measurements facilitate the elimination of the influence of extracerebral, systemic effects, a key problem in functional near-infrared spectroscopy (fNIRS) of the adult human brain. The analysis of measured time-of-flight distributions of photons often relies on moments or time windows. However, a systematic and quantitative characterization of the performance of these measurands is still lacking. Based on perturbation simulations for small localized absorption changes, we compared spatial sensitivity profiles and depth selectivity for moments (integral, mean time of flight and variance), photon counts in time windows and their ratios for different time windows. The influence of the instrument response function (IRF) was investigated for all measurands and for various source-detector separations. Variance exhibits the highest depth selectivity among the moments. Ratios of photon counts in different late time windows can achieve even higher selectivity. An advantage of moments is their robustness against the shape of the IRF and instrumental drifts.

Performance of measurands in time-domain optical brain imaging: depth selectivity versus contrast-to-noise ratio.

Time-domain optical brain imaging techniques introduce a number of different measurands for analyzing absorption changes located deep in the tissue, complicated by superficial absorption changes and noise. We implement a method that allows analysis, quantitative comparison and performance ranking of measurands under various conditions - including different values of reduced scattering coefficient, thickness of the superficial layer, and source-detector separation. Liquid phantom measurements and Monte Carlo simulations were carried out in two-layered geometry to acquire distributions of times of flight of photons and to calculate the total photon count, mean time of flight, variance, photon counts in time windows and ratios of photon counts in different time windows. Quantitative comparison of performance was based on objective metrics: relative contrast, contrast-to-noise ratio (CNR) and depth selectivity. Moreover, the product of CNR and depth selectivity was used to rank the overall performance and to determine the optimal source-detector separation for each measurand. Variance ranks the highest under all considered conditions.

Implementation of the extended Kalman filter for determining the optical and geometrical properties of turbid layered media by time-resolved single distance measurements.

In this article we propose an implementation of the extended Kalman filter (EKF) for the retrieval of optical and geometrical properties in two-layered turbid media assuming a dynamic setting, where absorption of each layer was changed in different steps. Prior works implemented the EKF in frequency-domain with several pairs of light sources and detectors and for static parameters estimation problems. Here we explore the use of the EKF in single distance, time-domain measurements, together with a corresponding forward model. Results show good agreement between retrieved and nominal values, with rather narrow analytical credibility intervals, indicating that the recovery process has low uncertainty, especially for the absorption coefficients.

Space-enhanced time-domain diffuse optics for determination of tissue optical properties in two-layered structures.

A novel methodology for solving the inverse problem of diffuse optics for two-layered structures is proposed to retrieve the absolute quantities of optical absorption and reduced scattering coefficients of the layers simultaneously. A liquid phantom with various optical absorption properties in the deep layer is prepared and experimentally investigated using the space-enhanced time-domain method. Monte-Carlo simulations are applied to analyze the different measurements in time domain, space domain, and by the new methodology. The deviations of retrieved values from nominal values of both layers' optical properties are simultaneously reduced to a very low extent compared to the single-domain methods. The reliability and uncertainty of the retrieval performance are also considerably improved by the new methodology. It is observed in time-domain analyses that for the deep layer the retrieval of absorption coefficient is almost not affected by the scattering properties and this kind of "deep scattering neutrality" is investigated and overcome as well.

Approaches for calibration and validation of near-infrared optical methods for oxygenation monitoring.

Pulse oximetry for arterial oxygenation monitoring and tissue oximetry for monitoring of cerebral oxygenation or muscle oxygenation are based on quantitative in vivo diffuse optical spectroscopy. However, in both cases the information on absolute or relative concentration of human tissue constituents and especially on hemoglobin oxygenation can often not be retrieved by model-based analysis. An in vivo calibration against an accepted reference measurement can be a practical alternative. Pulse oximeters and most of commercial cerebral tissue oximeters rely on empirical calibration based on invasive controlled human desaturation studies. As invasive in vivo tests on healthy subjects are ethically disputable and should be limited to exceptional cases this calibration practice is unsatisfactory. We present the current status and problems of calibration and validation in pulse oximetry and cerebral tissue oximetry including the pros and cons of in vivo as well as in vitro methods. We emphasize various digital and physical phantom approaches and discuss the prospects of their application and possible further developments.

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

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

Correction of an adding-doubling inversion algorithm for the measurement of the optical parameters of turbid media.

We present broadband measurements of the optical properties of tissue-mimicking solid phantoms using a single integrating sphere to measure the hemispherical reflectance and transmittance under a direct illumination at the normal incident angle. These measurements are traceable to reflectance and transmittance scales. An inversion routine using the output of the adding-doubling algorithm restricted to the reflectance and transmittance under a direct illumination was developed to produce the optical parameters of the sample along with an uncertainty budget at each wavelength. The results for two types of phantoms are compared to measurements by time-resolved approaches. The results between our method and these independent measurements agree within the estimated measurement uncertainties.

Fluorescence-guided surgery and intervention - An AAPM emerging technology blue paper.

Fluorescence-guided surgery (FGS) and other interventions are rapidly evolving as a class of technologically driven interventional approaches in which many surgical specialties visualize fluorescent molecular tracers or biomarkers through associated cameras or oculars to guide clinical decisions on pathological lesion detection and excision/ablation. The technology has been commercialized for some specific applications, but also presents technical challenges unique to optical imaging that could confound the utility of some interventional procedures where real-time decisions must be made. Accordingly, the AAPM has initiated the publication of this Blue Paper of The Emerging Technology Working Group (TETAWG) and the creation of a Task Group from the Therapy Physics Committee within the Treatment Delivery Subcommittee. In describing the relevant issues, this document outlines the key parameters, stakeholders, impacts, and outcomes of clinical FGS technology and its applications. The presentation is not intended to be conclusive, but rather to inform the field of medical physics and stimulate the discussions needed in the field with respect to a seemingly low-risk imaging technology that has high potential for significant therapeutic impact. This AAPM Task Group is working toward consensus around guidelines and standards for advancing the field safely and effectively.

M3BA: A Mobile, Modular, Multimodal Biosignal Acquisition Architecture for Miniaturized EEG-NIRS-Based Hybrid BCI and Monitoring.

OBJECTIVE: For the further development of the fields of telemedicine, neurotechnology, and brain-computer interfaces, advances in hybrid multimodal signal acquisition and processing technology are invaluable. Currently, there are no commonly available hybrid devices combining bioelectrical and biooptical neurophysiological measurements [here electroencephalography (EEG) and functional near-infrared spectroscopy (NIRS)]. Our objective was to design such an instrument in a miniaturized, customizable, and wireless form. METHODS: We present here the design and evaluation of a mobile, modular, multimodal biosignal acquisition architecture (M3BA) based on a high-performance analog front-end optimized for biopotential acquisition, a microcontroller, and our openNIRS technology. RESULTS: The designed M3BA modules are very small configurable high-precision and low-noise modules (EEG input referred noise @ 500 SPS 1.39 µVpp, NIRS noise equivalent power NEP750 nm = 5.92 pWpp, and NEP850 nm = 4.77 pWpp) with full input linearity, Bluetooth, 3-D accelerometer, and low power consumption. They support flexible user-specified biopotential reference setups and wireless body area/sensor network scenarios. CONCLUSION: Performance characterization and in-vivo experiments confirmed functionality and quality of the designed architecture. SIGNIFICANCE: Telemedicine and assistive neurotechnology scenarios will increasingly include wearable multimodal sensors in the future. The M3BA architecture can significantly facilitate future designs for research in these and other fields that rely on customized mobile hybrid biosignal modal biosignal acquisition architecture (M3BA), multimodal, near-infrared spectroscopy (NIRS), wireless body area network (WBAN), wireless body sensor network (WBSN).