Wavelength modulation diffuse optical imaging of the newborn infant brain

Worldwide, preterm birth and intrapartum events are the biggest causes of death and lifelong disability in children under 5 years of age, and often it is the lack of early diagnosis that leads to permanent damage. Perinatal arterial ischemic stroke (PAIS), for example, affects 1 in 2500 newborn infants and is a significant cause of lifelong disability. Despite being more common than large-artery stroke in adults, it is far less well understood. PAIS is also comparatively under-diagnosed, such that opportunities for timely treatment are often missed. While there have been major improvements in neonatal intensive care over the past 40 years, continuous monitoring of the brain remains rudimentary. We propose to evaluate an entirely new form of optical imaging, known as wavelength-modulation diffuse optical tomography (WM-DOT), for diagnosing and assessing PAIS and other forms of brain injury in newborn babies. It is safe, portable, low-cost, and easy to use. WM-DOT avoids dependency on variable surface effects and patient motion which have severely inhibited previous optical methods, and yields images which are sensitive to absolute rather than differences in optical properties. The images will reveal abnormalities in cerebral tissue oxygenation and thus lead to more prompt intervention, reducing incidence of permanent disability. Diffuse optical imaging involves illuminating the scalp with a harmless beam of light and measuring the amount of light that emerges after considerable scattering within the underlying tissues. The light is absorbed differently by the oxygenated and deoxygenated forms of haemoglobin (the molecule in blood that carries oxygen around the body), and thus these measurements are sensitive to the volume and oxygenation of blood. While methods known as near-infrared spectroscopy (NIRS) and diffuse optical tomography (DOT) have been explored as a means of brain monitoring of infants and adults for several decades, they are notoriously sensitive to the uncertain and variable coupling of light into and out of the skin surface (e.g. due to hair). Unknown coupling prevents the absolute concentrations of oxy- and deoxy-haemoglobin from being accurately derived, severely limiting clinical impact. Meanwhile, when a patient moves, relative motion between the optical probe and the head causes unpredictable coupling changes, producing imaging artefacts. Consequently, NIRS and DOT have been limited to measuring only changes in blood volume and oxygenation. The purpose of the proposed work is to establish a new optical imaging method, based on a light source whose wavelength (colour) is rapidly changed back-and-forth over a small range. Variation in the tissue absorption over this range will result in a small change in the amount of detected light as the wavelength is modulated. Measurements of the change in intensity as a proportion of the total amount of detected light are largely immune to variability in surface coupling and may allow derivation of the absolute quantities of absorbers in tissue. A prototype imaging device will be evaluated as a means of assessing a variety of newborn infant neuro-pathologies in a hospital intensive care unit. We will also work with an industrial partner to explore the development of the technology as a commercial product to accelerate its impact. A successful demonstration of WM-DOT will revolutionise the way NIRS and DOT are used in hospitals, and expand the range of medical applications of optical imaging technology, such as detection and assessment of adult stroke and other forms of brain injury.