A novel approach to monitor tissue oxygen saturation with broadband near-infrared spectroscopy

Cerebral oximetry is the measurement of tissue oxygen saturation, StO2, with near-infrared spectroscopy (NIRS). The technique offers a non-invasive assessment of cerebral oxygenation and has potential to be used as a biomarker in neonatal critical care, particularly hypoxic-ischaemic-encephalopathy (HIE). HIE is a major cause of neonatal mortality and affected neonates need continuous cerebral monitoring to guide treatment and improve patient outcome. While multiple algorithms to recover StO2 have been published, issues with low measurement accuracy or extracranial tissue signal contamination remain. This thesis is focused on the exploration of recovering StO2 from continuous-wave broadband NIRS measurements with the aim to develop a novel algorithm to recover StO2 with increased dynamic range and depth resolution. The novel algorithm, broadband multidistance oximetry (BRUNO), recovers StO2 from a broadband multidistance measurement of the attenuation slope against distance. BRUNO combines and expands two other StO2 algorithms, spatially resolved spectroscopy (SRS) and broadband fitting (BF). The evaluation of algorithm performance was done in data obtained in computational simulations and phantoms. The median error of brain StO2 recovered in simulations of brain and extracerebral tissue oxygenation changes was 1.1% with BRUNO, 2.3% with BF and 3.8% with SRS. Measurements during full oxygenation-deoxygenation cycles in a homogeneous blood phantom showed differences in the dynamic range of the algorithms; BRUNO recovered StO2 over 0–100%, BF over 0–90% and SRS over 40–80%. These results show higher accuracy of BRUNO StO2, higher sensitivity to brain oxygenation and wider dynamic range. Measurements of StO2 in one neonate with HIE showed that the StO2 algorithms led to different baseline values. Including an automated data assessment step in BRUNO to evaluate the suitability of collected spectra for analysis ensured BRUNO reliability. These findings highlight the effect of StO2 algorithm selection on oxygenation recovery; applying BRUNO in the clinical care setting could reveal further insight into complex oxygenation processes occurring during neonatal brain injury

Absolute quantification of cerebral tissue oxygen saturation with multidistance broadband NIRS in newborn brain

Tissue oximetry with near-infrared spectroscopy (NIRS) is a technique for the measurement of absolute tissue oxygen saturation (StO2). Offering a real-time and non-invasive assessment of brain oxygenation and haemodynamics, StO2 has potential to be used for the assessment of newborn brain injury. Multiple algorithms have been developed to measure StO2, however, issues with low measurement accuracy or extracranial tissue signal contamination remain. In this work, we present a novel algorithm to recover StO2 in the neonate, broadband multidistance oximetry (BRUNO), based on a measurement of the gradient of attenuation against distance measured with broadband NIRS. The performance of the algorithm was compared to two other published algorithms, broadband fitting (BF) and spatially resolved spectroscopy (SRS). The median error when recovering StO2 in light transport simulations on a neonatal head mesh was 0.4% with BRUNO, 4.2% with BF and 9.5% with SRS. BRUNO was more sensitive to brain tissue oxygenation changes, shown in layered head model simulations. Comparison of algorithm performance during full oxygenation-deoxygenation cycles in a homogeneous dynamic blood phantom showed significant differences in the dynamic range of the algorithms; BRUNO recovered StO2 over 0–100%, BF over 0–90% and SRS over 39–80%. Recovering StO2 from data collected in a neonate treated at the neonatal intensive care showed different baseline values; mean StO2 was 64.9% with BRUNO, 67.2% with BF and 73.2% with SRS. These findings highlight the effect of StO2 algorithm selection on oxygenation recovery; applying BRUNO in the clinical care setting could reveal further insight into complex haemodynamic processes occurring during neonatal brain injury

Investigation of Confounding Factors in Measuring Tissue Saturation with NIRS Spatially Resolved Spectroscopy

Performing absolute measurements of tissue saturation of the brain with near-infrared spectroscopy (NIRS) is a clinically desirable brain monitoring tool. Tissue oxygenation index (TOI) is an indicator of absolute tissue mixed arterial and venous oxygen saturation, and can be calculated using a NIRS technique called spatially resolved spectroscopy (SRS). SRS instruments measure the change of light attenuation with distance by using multiple light source-detector distances at two or more wavelengths. The aim of the study is to use broadband NIRS SRS data to investigate the effects on the calculation of TOI of different parameters: wavelength selection, scattering dependence, source-detector distance, and resolving for water. In total, 55 neonates with hypoxic-ischemic encephalopathy were monitored using a broadband multi-distance continuous wave NIRS system; 172 datasets were recorded. Using a “Standard” approach, TOI values between 0 and 100% (“good”) were calculated in 157/172 datasets with a mean TOI of 50%. By changing the wavelength selection, the number of “good” data sets increases to 165/172 with a mean of 60%. Alteration of the dependence of scattering on wavelength acts as a constant which shifts the absolute value of TOI significantly (p < 0.05), demonstrating the importance of having a subject-appropriate estimation of scattering dependence. In general, changing the combination of source-detector distances does not significantly alter the TOI (the mean TOI ranges from 41% to 53%) which suggests that the algorithm is robust to different source-detector combinations. The study shows the broadband NIRS SRS algorithm gives the opportunity to explore the calculation of TOI and could further improve the measurement of tissue saturation in a clinical setting

Viscous hydrophilic injection matrices for serial crystallography

Serial (femtosecond) crystallography at synchrotron and X-ray free-electron laser (XFEL) sources distributes the absorbed radiation dose over all crystals used for data collection and therefore allows measurement of radiation damage prone systems, including the use of microcrystals for room-temperature measurements. Serial crystallography relies on fast and efficient exchange of crystals upon X-ray exposure, which can be achieved using a variety of methods, including various injection techniques. The latter vary significantly in their flow rates – gas dynamic virtual nozzle based injectors provide very thin fast-flowing jets, whereas high-viscosity extrusion injectors produce much thicker streams with flow rates two to three orders of magnitude lower. High-viscosity extrusion results in much lower sample consumption, as its sample delivery speed is commensurate both with typical XFEL repetition rates and with data acquisition rates at synchrotron sources. An obvious viscous injection medium is lipidic cubic phase (LCP) as it is used for in meso membrane protein crystallization. However, LCP has limited compatibility with many crystallization conditions. While a few other viscous media have been described in the literature, there is an ongoing need to identify additional injection media for crystal embedding. Critical attributes are reliable injection properties and a broad chemical compatibility to accommodate samples as heterogeneous and sensitive as protein crystals. Here, the use of two novel hydro­gels as viscous injection matrices is described, namely sodium carb­oxy­methyl cellulose and the thermo-reversible block polymer Pluronic F-127. Both are compatible with various crystallization conditions and yield acceptable X-ray background. The stability and velocity of the extruded stream were also analysed and the dependence of the stream velocity on the flow rate was measured. In contrast with previously characterized injection media, both new matrices afford very stable adjustable streams suitable for time-resolved measurements

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

Multi-laboratory efforts for the standardization of performance assessment of diffuse optics instruments - The BitMap Exercise

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 multi-laboratory comparison of photon migration instruments and their performances – the BitMap Exercise

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

Cyclists’ hazard anticipation and performance

Two-wheeler vehicles (i.e., bicycles, mopeds, and motorcycles) are becoming increasingly popular in congested cities because of their small dimensions, low cost of use compared to cars, and their contribution to a healthy lifestyle. Even though the use of two-wheelers offers benefits, their low conspicuity, instability, and vulnerability of the users create safety risks. Due to their small size, two-wheelers tend to be overseen by other road users, especially at intersections. Furthermore, the stability of two-wheelers is easily affected by disturbances such as an uneven road surface. Moreover, the unprotected state of two-wheeler users contributes to a high risk of serious injuries once an accident happens. A better understanding of how crashes occur in the rider-vehicle-road system is needed....Biomechatronics & Human-Machine Contro