Cerebral oxygenation monitoring in neonates: improving and validating instrumentation

Abstract

The brain is a very vulnerable organ and damage to it is often followed by severe implications such as long-term disabilities and it may even lead to death. Cerebral oximetry by near-infrared spectroscopy (NIRS) has repeatedly been cited as promis- ing technology, potentially enabling clinicians to prevent these outcomes. Preterm neonates are likely to suffer from complications leading to brain damage and may thus benefit strongly from NIRS monitoring. Although a number of commercial NIRS oximeters are clinically approved, the method has not yet been widely established. Two of the major reasons for this are poor precision of instruments and that tissue oxygen haemoglobin saturation (StO 2 ) obtained from different oximeters and sensors are incomparable. This thesis addresses these two problems and provides solutions. OxyPrem was developed with the objective to provide an instrument with increased precision to clinicians. Two versions, OxyPrem v1.2 and v1.3, are introduced in this thesis and their performance is validated in vivo and in vitro. Both sensors are based on symmetric arrangement of light sources and detectors and employ a self-calibrating algorithm. OxyPrem v1.2 performed excellently in vivo in a precision assessment on the forearm of adults (repeatability = within-subject standard deviation (S w ) = 1.7 %). Repeata- bility in preterm neonates was S w = 3.3% which is still good, taking into account that S w in neonates is typically higher than in adults. An improved version of the instrument, OxyPrem v1.3, was assessed in vivo in neonates as well. The study demonstrated S w as good as 2.8 %. Simultaneous mea- surements with another OxyPrem v1.3 sensor and a pulse oximeter revealed unstable physiology in some neonates. In a second analysis without these confounding sub- jects, S w improved drastically to 1.9 % which is amongst the best precision values ever achieved for NIRS oximeters. To overcome the lack of comparability of different oximeters and sensors, we have performed several studies with liquid phantoms simulating optical properties of neona- tal brain tissue. We first conducted experiments with a simple, homogeneous phantom and then refined the set-up to model a more realistic two-layer geometry resembling skull and brain. Our studies showed substantially different StO 2 readings provided by different oximeters which, however, were mostly linearly related. With the improved set-up, we characterized a large number of commercially available oximeters and sen- sors and provided coefficients for their pairwise linear relation. The method showed good repeatability and helps establishing comparability. As neonates are a very heterogeneous group, we investigated the effect that a varia- tion in total haemoglobin concentration (c tHb ) has on StO 2 readings by NIRS oxime- ters. We found strong influence of c tHb on StO 2 while only OxyPrem v1.3 proved to be largely immune to this effect, which causes substantial uncertainty to readings of other instruments. As the presented phantom set-up is very versatile, we additionally investigated sev- eral other effects with slight adaptations. These showed that StO 2 readings were un- affected by a thin superficial layer, while sensitivity decreased substantially for a layer with 16 mm thickness. In another experiment, we did not observe a change in StO 2 readings for very thin clear layers such as oil on the skin of neonates, whereas thicker layers must be avoided. Partial placement of sensors on top of hair and birth marks may seriously flaw StO 2 of sensors without symmetric source-detector arrangement and self-calibrating algorithm. In summary, this thesis provides solutions to two of the problems mentioned most often in association with cerebral oxygenation monitoring by NIRS. We have intro- duced OxyPrem v1.2 and v1.3 and demonstrated superior precision of the instruments in vivo. OxyPrem v1.3 proved to be largely immune to variation in c tHb , which reduces this considerable uncertainty in StO 2 readings to a minimum. By a series of in vitro experiments with liquid phantoms we were able to establish comparability of different instruments and systematically assessed several types of influences to StO 2 readings.