Shedding Light on the Brain

infants sustain long-term disability due to brain injury at or around the time of birth. The most common causes are damage related to extreme prematurity or some interruption to blood (and therefore oxygen) supply to the brain. Similarly, traumatic brain injury is a leading cause of mortality in the first four decades of life. Although techniques such as magnetic resonance imaging (MRI) and positron emission tomography (PET) can be used to provide information on the structure and function of the brain they cannot be used on critically ill patients undergoing life support, particularly newborn infants. Non-invasive, bedside methods of studying the brain which can be used in an intensive care setting are of vital importance in helping us understand the mechanisms of brain damage and develop strategies to improve long-term neurological outcome. Since the original paper in 1977 describing the first in vivo measurements in an intact brain, near infrared (NIR) spectroscopy has been widely used to monitor oxygen and blood levels in biological tissue. In the NIR the major constituent of tissue, water, exhibits relatively low absorption [Figure 1(a)], enabling multiply scattered light to penetrate several centimetres into tissue allowing optical interrogation of layers below the surface, e.g. the human brain cortex. NIR spectroscopy exploits this relative transparency to make spectroscopic measurements of the concentration of two dominant tissue chromophores, oxyhaemoglobin (HbO2) and deoxyhaemoglobin (HHb), found in the blood [Figure 1(b)]. Another significant NIR chromophore is the enzyme oxidised cytochrome c oxidase (CCO) which provides information about the ultilisation of oxygen at a cellular level. Figure 1(c) shows the absorption spectra for the oxidised and reduced forms of this enzyme. Unlike haemoglobin, the total concentration of the enzyme is unlikely to change over the course of a measurement and the difference spectra is used provide information on cellular wellbeing. Spectroscopic measurements of tissue in the NIR therefore provide information about levels of blood oxygenation (from the relative amounts of HbO2 and HHb), blood volume [derived from the concentration of total haemoglobin (HbO2 + HHb)] and cellular oxygen metabolic status (from the relative amounts of oxidised and reduced CCO). These measurements have enabled a wide range of basic science and applied clinical questions to be addressed. A major advantage of the technique is its non-invasive and continuous nature—the light intensity levels used being well below those associated with tissue damage. Systems are portable and measurements can be made easily and repeatedly, by clinical staff at the bedside. Early NIR spectroscopy instrumentation used a single emitter and detector (optodes) allowing a specific region of the brain to be monitored. The geometry and relative transparency of the heads of premature infants led to the clinical application of NIR spectroscopy in the early 1980s to the investigation of neonatal brain damage. This allowed specific clinical questions to be addressed including the effects the drug administration and the relationship between the severity of brain injury and long-term neurodevelopmental outcome. By the early 1990s the application of NIR spectroscopy had extended to measurements in the adult brain. A major concern in performing measurements in adults is the contribution from tissues outside the brain, e.g. skin and skull, and this has been addressed using a combination of mathematical modelling and experimental methods. NIR spectroscopy has since been used to investigate a number of different adult patient groups including those with acute brain injury, stroke, depression, dementia and epilepsy. The high temporal resolution of NIR spectroscopy enables rapid changes in blood oxygenation and volume to be monitored (Figure 2). This feature led to one of the most important developments in NIR spectroscopy research— the measurement of changes in blood NIR in Medicine