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.

Validation and Comparison of Monte Carlo and Finite Element Method in Forward Modeling for Near Infrared Optical Tomography.

Near infrared optical tomography (NIROT) is a non-invasive imaging technique to provide physiological information e.g. the oxygenation of tissue. For image reconstruction in clinical and preclinical scenarios, models to accurately describe light propagation are needed. This work aims to assess the accuracy and efficiency of different models, which paves the way for an optimal design of model-based image reconstruction algorithms in NIROT for realistic tissue geometries and heterogeneities. Two popular simulators were evaluated: the Monte Carlo (MC) method based MCX and the finite element method (FEM) based Toast++. We compared simulated results with experimental data measured on a homogeneous silicone phantom with well-calibrated parameters. The laser light was focused on the center of the phantom surface and images were captured by a CCD camera in both reflection and transmission modes. For transmittance measurements, the two models showed good agreement. Both achieve a cosine similarity of ~99%. In contrast, for reflectance measurements, FEM results deviated more from the measured values than MC, yielding similarity values of 86% and 94%, respectively. This study recommends the use of MC for NIROT in reflection mode and both MC and FEM yield excellent results for transmission mode.

Smart Toolkit for Fluorescence Tomography: Simulation, Reconstruction, and Validation.

OBJECTIVE: Fluorescence molecular tomography (FMT) can provide valuable molecular information by mapping the bio-distribution of fluorescent reporter molecules in the intact organism. Various prototype FMT systems have been introduced during the past decade. However, none of them has evolved as a standard tool for routine biomedical research. The goal of this paper is to develop a software package that can automate the complete FMT reconstruction procedure. METHODS: We present smart toolkit for fluorescence tomography (STIFT), a comprehensive platform comprising three major protocols: 1) virtual FMT, i.e., forward modeling and reconstruction of simulated data; 2) control of actual FMT data acquisition; and 3) reconstruction of experimental FMT data. RESULTS: Both simulation and phantom experiments have shown robust reconstruction results for homogeneous and heterogeneous tissue-mimicking phantoms containing fluorescent inclusions. CONCLUSION: STIFT can be used for optimization of FMT experiments, in particular for optimizing illumination patterns. SIGNIFICANCE: This paper facilitates FMT experiments by bridging the gaps between simulation, actual experiments, and data reconstruction.

Cerebral hemodynamic responses in preterm-born neonates to visual stimulation: classification according to subgroups and analysis of frontotemporal-occipital functional connectivity.

How neurovascular coupling develops in preterm-born neonates has been largely neglected in scientific research. We measured visually evoked (flicker light) hemodynamic responses (HRs) in preterm-born neonates ( n = 25 , gestational age: 31.71 ± 3.37 weeks, postnatal age: 25.48 ± 23.94 days) at the visual cortex (VC) and left frontotemporal lobe (FTL) using functional near-infrared spectroscopy (fNIRS) neuroimaging. We found that the HR characteristics show a large intersubject variability but could be classified into three groups according to the changes of oxyhemoglobin concentration at the VC [(A) increase, (B) decrease, or (C) inconclusive]. In groups A and B, the HRs at the left FTL were correlated with those at the VC, indicating the presence of a frontotemporal-occipital functional connectivity. Neonates in group A had a higher weight at measurement compared to those in group B, and had the lowest baseline total hemoglobin concentration and hematocrit compared to group C. To the best of our knowledge, this is the first fNIRS study showing (1) that the HRs of preterm-born neonates need to be classified into subgroups, (2) that the subgroups differed in terms of weight at measurement, and (3) that HRs can be observed also at the FTL during visual stimulation. These findings add insights into how neurovascular coupling develops in preterm-born neonates.

Absorption spectra of early stool from preterm infants need to be considered in abdominal NIRS oximetry.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of the preterm infant. Low abdominal tissue oxygen saturation (StO2) measured by near-infrared spectroscopy (NIRS) oximetry may be an early sign of NEC relevant for treating or even preventing NEC. However, current commercial NIRS oximeters provide inaccurate StO2 readings because they neglect stool as an abdominal absorber. To tackle this problem, we determined the optical properties of faeces of preterm infants to enable a correct abdominal StO2 measurement. In 25 preterm born infants (median age 31 0/7 ± 2 1/7 weeks, weight 1478 ± 511 g), we measured their first five stool probes with a VIS/NIR spectrometer and calculated the optical properties using the Inverse Adding Doubling (IAD) method. We obtained two absorption spectra representing meconium and transitional stool. Probabilistic cluster analysis correctly classified 96 out of 107 stool probes. The faeces spectra need to be considered to enable correct abdominal StO2 measurements with NIRS oximetry.

Reference Ranges for Hemoglobin and Hematocrit Levels in Neonates as a Function of Gestational Age (22⁻42 Weeks) and Postnatal Age (0⁻29 Days): Mathematical Modeling.

Hematological values of neonates need to be interpreted taking into account the fact that the reference ranges depend on the age of the neonate. We aimed to derive two general mathematical models for reference ranges for hemoglobin concentration (cHb) and hematocrit (Hct) levels in neonates as a function of gestational age (GA) and postnatal age (PNA), since it is known that GA and PNA are independent factors determining cHb and Hct. For this purpose, cHb and Hct values from the data set of Henry and Christensen (2015, Clin. Perinatol., 42, 483⁻497) from about 100,000 neonates (GA: 22⁻42 weeks, PNA: 0⁻28 days) were used and general models with two quadratic functions were derived. To the best of our knowledge, the models we have developed are the first published ones to provide reference ranges for cHb and Hct for neonates incorporating the parallel dependence on GA and PNA.

Characterization of the optical properties of color pastes for the design of optical phantoms mimicking biological tissue.

Clinicians need a way to rapidly and reliably test the correct functioning of near-infrared spectroscopy (NIRS)-based oximeters. Therefore, optical phantoms for quality assessment of NIRS oximeters are needed. The fabrication of such phantoms that mimic the optical properties of biological tissue in the NIR range represents a challenge. To enable their development, the aim was to characterize the absorption and scattering spectra of different dyes. The optical properties of silicone SILPURAN 2420 with 11 color pastes of type ELASTOSIL were measured in the 500 to 1000 nm range by a spectrometer with an integrating sphere. In addition, two commercial frequency-domain NIRS devices, the ISS OxiplexTS and the ISS Imagent, were used to assess the optical properties at specific wavelengths. The evaluated colors present mostly features in the visible range below 650 nm, but two colors include peaks in the near-infrared region, simulating low tissue oxygenation values. These colors were used to create an optical phantom, which matched the designed StO2 value within an error of only 4%. This set of dyes already enables simulating many different spectra, thus achieving a first step on the way to a long-term stable comparison and validation method.

Synchronized Oscillations of Arterial Oxygen Saturation, Cerebral Tissue Oxygenation and Heart Rate in Preterm Neonates: Investigation of Long-Term Measurements with Multiple Einstein's Cross Wavelet Analysis.

BACKGROUND: In preterm neonates, the cardiovascular and cerebral vascular control is immature, making the brain vulnerable to an increased incidence of hypoxic and hyperoxic episodes. AIM: The aim of the study was to apply the recently developed multiple Einstein's cross wavelet analysis (MECWA) to quantify the coupling of fluctuations of peripherally measured arterial oxygen saturation (SpO2), cerebral tissue oxygen saturation (StO2) and heart rate (HR). METHODS: Two long-term measurements on preterm neonates with a gestational age at birth of 26.4 and 26.8 weeks and a postnatal age of 2.1 and 3.9 weeks were analyzed. MECWA was applied to SpO2, StO2 and HR. RESULTS: MECWA showed that the fluctuations of SpO2, StO2 and HR were synchronized in the low-frequency range with periods of ~1 h and ~0.5 h. The amplitudes of the synchronization frequencies were dependent on the individual neonate. DISCUSSION: MECWA is a useful novel tool to assess the coupling of physiological signals. The parameters determined by MECWA seem to be related to the chronobiological processes, as well as constant regulations of the cardiovascular and cerebral perfusion state. CONCLUSION: MECWA was able to identify long-term synchronization of the cardiovascular and cerebral perfusion state in preterm neonates with periods of ~1 h and ~0.5 h.

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%.

Liquid Blood Phantoms to Validate NIRS Oximeters: Yeast Versus Nitrogen for Deoxygenation.

Liquid blood phantoms are a tool to calibrate, test and compare near-infrared spectroscopy (NIRS) oximeters. They comprise a mixture of saline, blood and Intralipid, which is subsequently oxygenated and deoxygenated to assess the entire range of tissue oxygen saturation (StO2) from 0% to 100%. The aim was to investigate two different deoxygenation methods: yeast versus nitrogen (N2) bubbling. The phantom was oxygenated with pure O2 in both experiments, but deoxygenated by bubbling N2 in the first and by addition of yeast and glucose in the second experiment. A frequency domain NIRS instrument (OxiplexTS) was used as reference and to monitor changes in the reduced scattering coefficient (µs') of the phantom. Both deoxygenation methods yielded comparable StO2 values. The deoxygenation was slower by a factor 2.8 and µs' decreased faster when bubbling N2. The constant bubbling of N2 mechanically stresses the Intralipid emulsion and causes a decrease in µs', probably due to aggregation of lipid droplets. Deoxygenation by N2 requires a more complex, air tight phantom. The gas flow cools the liquid and temperature needs to be monitored more closely. Consequently, we recommend using yeast for phantom deoxygenation.

In vivo precision assessment of a near-infrared spectroscopy-based tissue oximeter (OxyPrem v1.3) in neonates considering systemic hemodynamic fluctuations.

The aim was to determine the precision of a noninvasive near-infrared spectroscopy (NIRS)-based tissue oximeter (OxyPrem v1.3). Using a linear mixed-effects model, we quantified the variability for cerebral tissue oxygenation (StO2) measurements in 35 preterm neonates to be 2.64%, a value that meets the often-articulated clinicians' demand for a precise tissue oxygenation measurement. We showed that the variability of StO2 values measured was dominated by spontaneous systemic hemodynamic fluctuations during the measurement, meaning that precision of the instrument was actually even better. Based on simultaneous and continuous measurements of peripheral arterial oxygenation and cerebral StO2 with a second sensor, we were able to determine and quantify the physiological instability precisely. We presented different methods and analyses aiming at reducing this systematic physiological error of in vivo precision assessments. Using these methods, we estimated the precision of the OxyPrem tissue oximeter to be ≤ 1.85 % . With our study, we deliver relevant information to establish highly precise cerebral oxygenation measurements with NIRS-based oximetry, facilitating the further development toward a substantially improved diagnosis and treatment of patients with respect to brain oxygenation.

Optical properties of mice's stool in 550 to 1000 nm wavelength range.

The aim of this work was to measure optical properties of stool of mice to provide this relevant wavelength-dependent behavior for optical imaging modalities such as fluorescent molecular tomography and near-infrared optical tomography. BALB/c nude female mice were studied and optical properties of the stool were determined by employing the inverse adding-doubling approach. The animals were kept on chlorophyll-free diet. Nine stool samples were measured. The wavelength-dependent behavior of absorption and scattering in 550 to 1000 nm range is presented. The reduced scattering spectrum is fitted to the Mie scattering approximation in the near-infrared (NIR) wavelength range and to the Mie + Rayleigh approximation in visible/NIR range with the fitting coefficients presented. The study revealed that the absorption spectrum of stool can lead to crosstalk with the spectrum of hemoglobin in the NIR range.