Stefan Kleiser

A review on continuous wave functional near-infrared spectroscopy and imaging instrumentation and methodology

This year marks the 20th anniversary of functional near-infrared spectroscopy and imaging (fNIRS/fNIRI). As the vast majority of commercial instruments developed until now are based on continuous wave technology, the aim of this publication is to review the current state of instrumentation and methodology of continuous wave fNIRI. For this purpose we provide an overview of the commercially available instruments and address instrumental aspects such as light sources, detectors and sensor arrangements. Methodological aspects, algorithms to calculate the concentrations of oxy- and deoxyhemoglobin and approaches for data analysis are also reviewed. From the single-location measurements of the early years, instrumentation has progressed to imaging initially in two dimensions (topography) and then three (tomography). The methods of analysis have also changed tremendously, from the simple modified Beer-Lambert law to sophisticated image reconstruction and data analysis methods used today. Due to these advances, fNIRI has become a modality that is widely used in neuroscience research and several manufacturers provide commercial instrumentation. It seems likely that fNIRI will become a clinical tool in the foreseeable future, which will enable diagnosis in single subjects.

A review of near infrared spectroscopy for term and preterm newborns

This article reviews the application of near infrared (NIR) spectroscopy in preterm and newborn infants and its clinical value. After an overview of the commercially available instrumentation, which is able to provide absolute values of tissue haemoglobin saturation (StO2), we focus on the application of NIR spectroscopy to measure brain, liver, gastro-intestinal and peripheral oxygenation. From the instrumentation point of view, NIR spectroscopy has gained significantly in clinical importance, especially by being able to measure StO2, i.e. an absolute parameter. An increasing number of commercial instruments is available today and the number of users is virtually exploding. However, the precision of the measurements is still too low from a clinical point of view and the variety of algorithms employed by the different instruments and sensors may provide quite different StO2 values. In the future, the different instruments need to report quantitatively comparable StO2 measurements which are more precise. The measurement of cerebral StO2 may be useful for detecting situations where the oxygenation of the brain may be impaired and the hope is that this indicates situations which lead to brain lesions. However, the clinical utility of cerebral StO2 still needs to be examined. Although liver and gastro-intestinal as well as peripheral measurements are still an object of research and several problems have to be overcome before clinical use, these measurements could be of high value in specific clinical situations.

Textile integrated sensors and actuators for near-infrared spectroscopy

Being the closest layer to our body, textiles provide an ideal platform for integrating sensors and actuators to monitor physiological signals. We used a woven textile to integrate photodiodes and light emitting diodes. LEDs and photodiodes enable near-infrared spectroscopy (NIRS) systems to monitor arterial oxygen saturation and oxygenated and deoxygenated hemoglobin in human tissue. Photodiodes and LEDs are mounted on flexible plastic strips with widths of 4 mm and 2 mm, respectively. The strips are woven during the textile fabrication process in weft direction and interconnected with copper wires with a diameter of 71 μm in warp direction. The sensor textile is applied to measure the pulse waves in the fingertip and the changes in oxygenated and deoxygenated hemoglobin during a venous occlusion at the calf. The system has a signal-to-noise ratio of more than 70 dB and a system drift of 0.37% ± 0.48%. The presented work demonstrates the feasibility of integrating photodiodes and LEDs into woven textiles, a step towards wearable health monitoring devices.

Calibration of a prototype NIRS oximeter against two commercial devices on a blood-lipid phantom

In a blood-lipid liquid phantom the prototype near-infrared spectroscopy oximeter OxyPrem was calibrated against the INVOS® 5100c adult sensor in respect to values of regional tissue oxygen haemoglobin saturation (rStO2) for possible inclusion in the randomised clinical trial - SafeBoosC. In addition different commercial NIRS oximeters were compared on changing haemoglobin oxygen saturation and compared against co-oximetry. The best calibration was achieved with a simple offset and a linear scaling of the OxyPrem rStO2 values. The INVOS adult and pediatric sensor gave systematically different values, while the difference between the NIRO® 300 and the two INVOS sensors were magnitude dependent. The co-oximetry proved unreliable on such low haemoglobin and high Intralipid levels.

Comparison of tissue oximeters on a liquid phantom with adjustable optical properties

The SafeBoosC trial showed that cerebral oximetry combined with a treatment guideline can reduce the the burden of hypoxia in neonates by 50% [Brit. Med. J.350, g7635 (2015)]. However, guidelines based on oximetry by one oximeter are not directly usable by other oximeters. We made a blood-lipid phantom simulating the neonatal head to determine the relation between oxygenation values obtained by different oximeters. We calculated coefficients for easy conversion from one oximeter to the other. We additionally determined the corresponding SafeBoosC intervention thresholds at which we measured an uncertainty of up to 9.2% when varying hemoglobin content from 25μM to 70μM. In conclusion, this paper makes the comparison of absolute values obtained by different oximeters possible.

Quantifying the effect of adipose tissue in muscle oximetry by near infrared spectroscopy

Change of muscle tissue oxygen saturation (StO2), due to exercise, measured by near infrared spectroscopy (NIRS) is known to be lower for subjects with higher adipose tissue thickness. This is most likely not physiological but caused by the superficial fat and adipose tissue. In this paper we assessed, in vitro, the influence of adipose tissue thickness on muscle StO2, measured by NIRS oximeters. We measured StO2 of a liquid phantom by 3 continuous wave (CW) oximeters (Sensmart Model X-100 Universal Oximetry System, INVOS 5100C, and OxyPrem v1.3), as well as a frequency-domain oximeter, OxiplexTS, through superficial layers with 4 different thicknesses. Later, we employed the results to calibrate OxyPrem v1.3 for adipose tissue thickness in-vivo.

Comparison of Near-Infrared Oximeters in a Liquid Optical Phantom with Varying Intralipid and Blood Content.

The interpretation of cerebral tissue oxygen saturation values (StO2) in clinical settings is currently complicated by the use of different near-infrared spectrophotometry (NIRS) devices producing different StO2 values for the same oxygenation due to differences in the algorithms and technical aspects. The aim was to investigate the effect of changes in scattering and absorption on the StO2 of different NIRS devices in a liquid optical phantom. We compared three continuous-wave (CW) with a frequency domain (FD) NIRS device. Responsiveness to oxygenation changes was only slightly altered by different intralipid (IL) concentrations. However, alterations in haematocrit (htc) showed a strong effect: increased htc led to a 20-35% increased response of all CW devices compared to the FD device, probably due to differences in algorithms regarding the water concentration.

Characterizing Fluctuations of Arterial and Cerebral Tissue Oxygenation in Preterm Neonates by Means of Data Analysis Techniques for Nonlinear Dynamical Systems.

The cerebral autoregulatory state as well as fluctuations in arterial (SpO2) and cerebral tissue oxygen saturation (StO2) are potentially new relevant clinical parameters in preterm neonates. The aim of the present study was to test the investigative capabilities of data analysis techniques for nonlinear dynamical systems, looking at fluctuations and their interdependence. StO2, SpO2 and the heart rate (HR) were measured on four preterm neonates for several hours. The fractional tissue oxygenation extraction (FTOE) was calculated. To characterize the fluctuations in StO2, SpO2, FTOE and HR, two methods were employed: (1) phase-space modeling and application of the recurrence quantification analysis (RQA), and (2) maximum entropy spectral analysis (MESA). The correlation between StO2 and SpO2 as well as FTOE and HR was quantified by (1) nonparametric nonlinear regression based on the alternating conditional expectation (ACE) algorithm, and (2) the maximal information-based nonparametric exploration (MINE) technique. We found that (1) each neonate showed individual characteristics, (2) a ~60 min oscillation was observed in all of the signals, (3) the nonlinear correlation strength between StO2 and SpO2 as well as FTOE and HR was specific for each neonate and showed a high value for a neonate with a reduced health status, possibly indicating an impaired cerebral autoregulation. In conclusion, our data analysis framework enabled novel insights into the characteristics of hemodynamic and oxygenation changes in preterm infants. To the best of our knowledge, this is the first application of RQA, MESA, ACE and MINE to human StO2 data measured with near-infrared spectroscopy (NIRS).

Comparison of tissue oximeters on a liquid phantom with adjustable optical properties: an extension

Cerebral near-infrared spectroscopy (NIRS) oximetry may help clinicians to improve patient treatment. However, the application of NIRS oximeters is increasingly causing confusion to the users due to the inconsistency of tissue oxygen haemoglobin saturation (StO2) readings provided by different oximeters. To establish a comparability of oximeters, in our study we performed simultaneous measurements on the liquid phantom mimicking properties of neonatal heads and compared the tested device to a reference NIRS oximeter (OxiplexTS). We evaluated the NIRS oximeters FORE-SIGHT, NIRO and SenSmart, and reproduced previous results with the INVOS and OxyPrem v1.3 oximeters. In general, linear relationships of the StO2 values with respect to the reference were obtained. Device specific hypoxic and hyperoxic thresholds (as used in the SafeBoosC study, www.safeboosc.eu) and a table allowing for conversion of StO2 values are provided.

Simulation of Preterm Neonatal Brain Metabolism During Functional Neuronal Activation Using a Computational Model

We present a computational model of metabolism in the preterm neonatal brain. The model has the capacity to mimic haemodynamic and metabolic changes during functional activation and simulate functional near-infrared spectroscopy (fNIRS) data. As an initial test of the model’s efficacy, we simulate data obtained from published studies investigating functional activity in preterm neonates. In addition we simulated recently collected data from preterm neonates during visual activation. The model is well able to predict the haemodynamic and metabolic changes from these observations. In particular, we found that changes in cerebral blood flow and blood pressure may account for the observed variability of the magnitude and sign of stimulus-evoked haemodynamic changes reported in preterm infants.