Clinical applications of near-infrared spectroscopy in neonates

Key points

The status of cerebral oxygenation is not always represented appropriately by systemic arterial oxygenation, especially when there are changes in cerebral blood flow or cardiac output. Oxygenation monitoring of the brain by near-infrared spectroscopy (NIRS) is therefore an important additive measure in neonatal intensive care.
Monitoring cerebral oxygenation by NIRS, in addition to arterial saturation monitoring by pulse oximetry, blood pressure, and brain function by aEEG, can help to prevent brain damage as well as prevent unnecessary treatment of the neonate.
Cerebral oxygenation can be stabilized in the neonate using a dedicated treatment guideline in combination with cerebral oxygenation monitoring by NIRS.

Introduction

Survival of the extremely preterm infant has greatly improved over the past decades. However, perinatal brain damage with adverse neurodevelopmental outcome continues to affect a considerable number of these infants. Although the etiology of brain damage is multi-factorial and partly unknown (see Chapter 7 ), hypoxia, hyperoxia, specific and non-specific inflammation, and hemodynamic instability during the first days of postnatal life play an important role. It is clear that further advances in survival and improvements in neurodevelopmental outcome can only be achieved if we learn more about the underlying pathophysiology so that more effective treatment modalities can be established. The first step in this direction is to develop the capability to continuously monitor clinically relevant hemodynamic variables and, if possible, treat the underlying condition at an early stage. Continuous monitoring of physiological parameters such as heart rate, blood pressure, arterial oxygen saturation (SaO ₂ ), temperature, and, with increasing frequency, electrical activity of the brain using amplitude-integrated EEG (aEEG) have been integrated into the monitoring practices of neonatal intensive care units (NICUs). aEEG has been introduced into neonatal intensive care as a novel monitoring technique to continuously assess cerebral electric activity. Both the aEEG background patterns and the analysis of the raw EEG signal have been used for the evaluation of neurological function. The fewer channels compared to the classic full EEG improves its applicability, and the use of aEEG has increased. ^, Other, novel techniques used to continuously monitor additional hemodynamic parameters, such as cardiac output, are discussed in Chapter 9, Chapter 10, Chapter 11 in detail.

Intermittent tools to assess cerebral health, such as cranial ultrasound, Doppler flow velocity measurements, and (advanced) magnetic resonance imaging (MRI), have also been integrated into the care of the sick neonate (see Chapter 11, Chapter 12, Chapter 13 for details). These techniques, however, do not provide continuous information on the perfusion and oxygenation of the neonatal brain.

Therefore we need a reliable and practical clinical tool that monitors oxygenation of the neonatal brain noninvasively and continuously so that conditions potentially leading to brain injury can be recognized in a timely manner. An increasingly clinically used method is monitoring cerebral oxygenation by NIRS.

Principles of near-infrared spectroscopy

Near-infrared (NIR) spectroscopy technology utilizes light in the near-infrared range (700–1000 nm). NIR spectroscopy instrumentation consists of fiber optic bundles or optodes placed either on opposite sides of the tissue being interrogated (usually a limb or the head of a baby) to measure transmitted light or close together to measure reflected light. NIR-light (laser or, more frequently, LED light) enters through one optode and a fraction of the photons are captured by a second optode and conveyed to a measuring device.

Jöbsis first introduced the use of NIR spectrophotometers for human tissue in 1977. Human tissues contain a variety of substances whose absorption spectra at NIR wavelengths are well defined. They are present in sufficient quantities to contribute significant attenuation to measurements of transmitted light. The concentration of some absorbers such as water, melanin, and bilirubin remains virtually constant with time. However, the concentrations of some absorbing compounds, such as oxygenated hemoglobin (HbO ₂ ) and deoxyhemoglobin (HbR), vary with tissue oxygenation. Therefore changes in light absorption can be related to changes in the concentrations of these compounds.

The absorption properties of hemoglobin alter when it changes from its oxygenated to its deoxygenated form. In the NIR region of the spectrum the absorption of the hemoglobin chromophores (HbR and HbO ₂ ) decreases significantly compared to that observed in the visible region. The major part of the NIR spectroscopy signal is derived from hemoglobin, but other hemoglobin compounds, such as carboxyhemoglobin, also absorb light in the NIR region. However, the combined error due to ignoring these compounds in the measurement of the total hemoglobin signal is probably less than 1% in normal blood.

Near-infrared spectrophotometers

Three different methods of using NIR light for monitoring tissue oxygenation are currently used: continuous wave, time-of-flight (also known as time-domain or time-resolved), and the frequency domain methods. For an extensive overview of the methods, we refer the reader to Wolf et al. The continuous wave method has a very fast response but registers relative change only, and it is therefore not possible to make absolute measurements using this technique. The time-of-flight method needs extensive data processing but provides more accurate measurements. It enables one to explore different information provided by the measured signals and has the potential to become a valuable tool in research and clinical environments. The third approach , which uses frequency domain or phase modulation technology, has a lower resolution than that of the time-of-flight method but has the potential to provide estimates of oxygen delivery sufficiently quickly for clinical purposes. Thus frequency domain or phase modulation technology is potentially the best candidate in the NICU and for bedside usage. Nevertheless, the continuous wave method devices have been widely used for research studies. ^,

Continuous wave spectroscopy

In continuous wave spectroscopy changes in tissue chromophore concentrations from the baseline value can be obtained from the modified Beer-Lambert law . However, the application of the Beer-Lambert law in its original form has limitations. Its linearity is limited by deviation in the absorption coefficient at high concentrations, scattering of light due to particulate matter in the sample, and ambient light.

Thus for light passing through a highly scattering medium, the Beer-Lambert law has been modified to include an additive term, K , due to scattering losses, and a multiplier to account for the increased optical pathlength due to scattering.

The modified Beer-Lambert law is expressed as A = P × L × E × C + K, where A is absorbance, P is the pathlength factor, L is the path length, E is the extinction coefficient, C is the concentration of the compound, and K is a constant. The differential pathlength factor describes the actual distance traveled by light. As it is dependent on the amount of scattering in the medium, its measurement is not straightforward. Examples of instruments using continuous wave technology are the NIRO 500 and NIRO 100, made by Hamamatsu Photonic, Hamamatsu, Japan.

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