Self-calibrating time-resolved near infrared spectroscopy

Time-resolved near infrared spectroscopy is considered to be a gold standard technique when measuring absolute values of tissue optical properties, as it provides separable and independent information about both tissue absorption and scattering. However, time-resolved instruments require an accurate characterization by measuring the instrument response function in order to decouple the contribution of the instrument itself from the measurement. In this work, a new approach to the methodology of analysing time-resolved data is presented where the influence of instrument response function is eliminated from the data and a self-calibrating analysis is proposed. The proposed methodology requires an instrument to provide at least two wavelengths and allows spectral parameters recovery (optical properties or constituents concentrations and reduced scatter amplitude and power). Phantom and in-vivo data from two different time-resolved systems are used to validate the accuracy of the proposed self-calibrating approach, demonstrating that parameters recovery compared to the conventional curve fitting approach is within 10% and benefits from introducing a spectral constraint to the reconstruction problem. It is shown that a multiwavelength time-resolved data can be used for parameters recovery directly without prior calibration (instrument response function measurement)

Multi-laboratory performance assessment of diffuse optics instruments: the BitMap exercise

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

Modern methods of assessment of lung aeration during mechanical ventilation

Despite the fact that several modes of ventilation are being used, it is not always possible to maintain adequate parameters of gas exchange. In order to provide proper ventilation, it is necessary to assess the lung function. The aim of this article is presentation of different methods of assesment of lung aerations including its advantages, disadvantages and possibilities for implementation in clinical practice. Computed tomography provides information regarding morphology and aeration of lung tissue, but has several limitations: necessity of patients transportation, it cannot be performed in a continuous manner, a quantitative assessment of picture seems to be rather complicated. Ultrasonography is widely used in intensive care and is a noninvasive and bedside method. It gives the opportunity to assess an investigated organ in real time. Its clinical utility in patients with ARDS was proved by Lichtenstein et al. Another technology which has been implemented for the purpose of lungs visualization is electrobioimpedancy (EIT). This new method consists of continuous monitoring of chest electrobioimpedancy changes due to its air content. Unlike to techniques mentioned above, lung images generated with EIT do not provide any information about morphology of affected tissue. The method which indirectly describes the sum of lung interactions is the assessment of quasi-static P/V curve. This method provides information allowing to draw conclusions regarding the usefulness of recruitment maneuvers, but does not provide information regarding the nature of morphologic changes and their location. In the search for the ideal method of lung aeration assessment, it is necessary to define its characteristics, such as noninvasiveness, availability and visualization of tissue morphologic changes in real time.Despite the fact that several modes of ventilation are being used, it is not always possible to maintain adequate parameters of gas exchange. In order to provide proper ventilation, it is necessary to assess the lung function. The aim of this article is presentation of different methods of assesment of lung aerations including its advantages, disadvantages and possibilities for implementation in clinical practice. Computed tomography provides information regarding morphology and aeration of lung tissue, but has several limitations: necessity of patients transportation, it cannot be performed in a continuous manner, a quantitative assessment of picture seems to be rather complicated. Ultrasonography is widely used in intensive care and is a noninvasive and bedside method. It gives the opportunity to assess an investigated organ in real time. Its clinical utility in patients with ARDS was proved by Lichtenstein et al. Another technology which has been implemented for the purpose of lungs visualization is electrobioimpedancy (EIT). This new method consists of continuous monitoring of chest electrobioimpedancy changes due to its air content. Unlike to techniques mentioned above, lung images generated with EIT do not provide any information about morphology of affected tissue. The method which indirectly describes the sum of lung interactions is the assessment of quasi-static P/V curve. This method provides information allowing to draw conclusions regarding the usefulness of recruitment maneuvers, but does not provide information regarding the nature of morphologic changes and their location. In the search for the ideal method of lung aeration assessment, it is necessary to define its characteristics, such as noninvasiveness, availability and visualization of tissue morphologic changes in real time

Frequency analysis of oscillations in cerebral hemodynamics measured by time domain near infrared spectroscopy

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

Time-domain NIRS system based on supercontinuum light source and multi-wavelength detection: validation for tissue oxygenation studies

We present and validate a multi-wavelength time-domain near-infrared spectroscopy (TD-NIRS) system that avoids switching wavelengths and instead exploits the full capability of a supercontinuum light source by emitting and acquiring signals for the whole chosen range of wavelengths. The system was designed for muscle and brain oxygenation monitoring in a clinical environment. A pulsed supercontinuum laser emits broadband light and each of two detection modules acquires the distributions of times of flight of photons (DTOFs) for 16 spectral channels (used width 12.5 nm / channel), providing a total of 32 DTOFs at up to 3 Hz. Two emitting fibers and two detection fiber bundles allow simultaneous measurements at two positions on the tissue or at two source-detector separations. Three established protocols (BIP, MEDPHOT, and nEUROPt) were used to quantitatively assess the system's performance, including linearity, coupling, accuracy, and depth sensitivity. Measurements were performed on 32 homogeneous phantoms and two inhomogeneous phantoms (solid and liquid). Furthermore, measurements on two blood-lipid phantoms with a varied amount of blood and Intralipid provide the strongest validation for accurate tissue oximetry. The retrieved hemoglobin concentrations and oxygen saturation match well with the reference values that were obtained using a commercially available NIRS system (OxiplexTS) and a blood gas analyzer (ABL90 FLEX), except a discrepancy occurs for the lowest amount of Intralipid. In-vivo measurements on the forearm of three healthy volunteers during arterial (250 mmHg) and venous (60 mmHg) cuff occlusions provide an example of tissue monitoring during the expected hemodynamic changes that follow previously well-described physiologies. All results, including quantitative parameters, can be compared to other systems that report similar tests. Overall, the presented TD-NIRS system has an exemplary performance evaluated with state-of-the-art performance assessment methods

Application of optical methods in the monitoring of traumatic brain injury : A review

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

Confirmation of brain death using optical methods based on tracking of an optical contrast agent : assessment of diagnostic feasibility

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 &lt; 0.0001). Depending on the combination of variables used in the OPLS-DA model, sensitivity, specificity, and accuracy were 66.7-92.9%, 81.8-92.9%, and 77.3-89.3%, respectively. The method was feasible and promising in the demanding intensive care unit environment. However, its accuracy did not reach the level required for brain death confirmation. The potential usefulness of the method may be improved by increasing the depth of light penetration, confirming its accuracy against other methods evaluating cerebral flow cessation, and developing absolute parameters for cerebral perfusion

Effect of Antimony Buffer Layer on the Electric and Magnetic Properties of 200 and 600 nm Thick Bismuth Films on Mica Substrate

We report on the production of 200 and 600 nm thick Bi films on mica substrate with 10 nm thick Sb sublayer between Bi and mica. Two types of films have been studied: block and single crystal. Films were obtained using the thermal evaporation technique using continuous and discrete spraying. Discrete spraying allows smaller film blocks size: 2&ndash;6 &mu; m compared to 10&ndash;30 &mu; m, obtained by the continuous spraying. Single crystal films were made by the zone recrystallization method. Microscopic examination of Bi films with and without Sb sublayer did not reveal an essential distinction in crystal structure. A galvanomagnetic study shows that Sb sublayer results in the change of Bi films properties. Sb sublayer results in the increase of specific resistivity of block films and has no significant impact on single crystal films. For single-crystal films with Sb sublayer with a thickness of 200 nm the Hall coefficient has value 1.5 times higher than for the 600 nm thickness films at 77 K. The change of the Hall coefficient points to change of the contribution of carriers in the conductivity. This fact indicates a change in the energy band structure of the thin Bi film. The most significant impact of the Sb sublayer is on the magnetoresistance of single-crystal films at low temperatures. The increase of magnetoresistance points to the increase of mobility of the charge carriers. In case of detecting and sensing applications the increased carriers mobility can result in a faster device response time

BRAF Mutation, NRAS Mutation, and the Absence of an Immune-Related Expressed Gene Profile Predict Poor Outcome in Patients with Stage III Melanoma

Prediction of outcome for melanoma patients with surgically resected macroscopic nodal metastases is very imprecise. We performed a comprehensive clinico-pathologic assessment of fresh-frozen macroscopic nodal metastases and the preceding primary melanoma, somatic mutation profiling, and gene expression profiling to identify determinants of outcome in 79 melanoma patients. In addition to disease stage <II at initial presentation, the following clinical and pathologic factors were independent predictors of improved outcome (odds ratios for survival >4 years, 90% confidence interval): the presence of a nodular component in the primary melanoma (6.8, 0.6–76.0), and small cell size (11.1, 0.8–100.0) or low pigmentation (3.0, 0.8–100.0) in the nodal metastases. Absence of BRAF mutation (20.0, 1.0–1000.0) or NRAS mutation (16.7, 0.6–1000.0) were both favorable prognostic factors. A 46-gene expression signature with strong overrepresentation of immune response genes was predictive of better survival (10.9, 0.4–325.6); in the full cohort, median survival was >100 months in those with the signature, but 10 months in those without. This relationship was validated in two previously published independent stage III melanoma data sets. We conclude that the presence of BRAF mutation, NRAS mutation, and the absence of an immune-related expressed gene profile predict poor outcome in melanoma patients with macroscopic stage III disease