Diffuse optical tomography to investigate the newborn brain
Abstract
Over the past 15 years, functional near-infrared spectroscopy (fNIRS) has emerged as a powerful technology for studying the developing brain. Diffuse optical tomography (DOT) is an extension of fNIRS that combines hemodynamic information from dense optical sensor arrays over a wide field of view. Using image reconstruction techniques, DOT can provide images of the hemodynamic correlates to neural function that are comparable to those produced by functional magnetic resonance imaging. This review article explains the principles of DOT, and highlights the growing literature on the use of DOT in the study of healthy development of the infant brain, and the study of novel pathophysiology in infants with brain injury. Current challenges, particularly around instrumentation and image reconstruction, will be discussed, as will the future of this growing field, with particular focus on whole-brain, time-resolved DOT.
Main
The field of medical physics and biomedical engineering has provided a range of novel neuroimaging techniques that have enabled scientists and clinicians to investigate the functional organization and architecture of the human brain in health and disease. In recent years, functional near-infrared spectroscopy (fNIRS) has become an increasingly valuable tool. In addition to being non-invasive, relatively low-cost and easy to set up, it can be carried out in infants who are awake and do not need to be transported to specialized imaging facilities. Diffuse optical tomography (DOT) is a natural extension of fNIRS, which combines multi-channel data acquisition with image reconstruction software to provide images of changes in regional blood volume and oxygenation at high temporal and spatial resolution. This technology is increasingly being used by researchers and clinicians to study healthy brain development, as well as pathophysiology in critically ill infants in intensive care. Figure 1 summarizes the terminology and NIRS domains that will be described in this paper.
Figure 1
A decision tree that provides a definition of the different forms of diffuse optical monitoring. Although nomenclature varies across the field, these are the definitions preferred by the authors. 2D, two dimensional; NIRS, near-infrared spectroscopy.
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The aim of this paper is to explain the principles of DOT and highlight studies using DOT in newborn infants. We also summarize the current challenges of the technique and discuss the future of the field, with particular emphasis on technological developments and time-domain DOT (TD-DOT) techniques.
Principles of optical imaging
Near-Infrared Spectroscopy
NIRS is a non-invasive tissue-monitoring technique that exploits the relative transparency of biological tissue to near-infrared (NIR) light (650–950 nm) and the wavelength-dependent absorption characteristics of light-absorbing compounds or chromophores. In the brain, hemoglobin is the dominant chromophore, whose absorption varies with oxygenation—first described by Jöbsis (1, 2, 3) (Figure 2a).
Figure 2
Principles and practical aspects of diffuse optical tomography. (a) The absorption properties of oxyhemoglobin (red line), deoxyhemoglobin (green line), and water (blue line) in biological tissue. In the optical window (shaded in blue) between 700 and 900 nm, light is relatively transparent as the absorption by water molecules is relatively low compared with oxyhemoglobin and deoxyhemoglobin. (b) The path of near-infrared light from an optical source follows a banana shape, as it travels in cerebral tissue before the transmitted light is measured at the detector (84). (c) The UCL Optical Imaging System (Gowerlabs, London, UK). This is a continuous-wave device that samples at 10 Hz and provides 16 optical sources and 16 detectors. (d) An example of headgear design used in infant studies of whole-head diffuse optical tomography.
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However, the dominant interaction between NIR light and tissue is not absorption but scattering, such that the path traveled by a given photon will constitute a ‘random walk’: bouncing randomly from one scattering event to the next. NIR light therefore forms a diffuse field when entering tissue. Assuming that scattering remains constant, loss of light, or attenuation, will be because of changes in absorption by the main chromophores (light-absorbing molecules). The simplest form of NIRS measurement consists of two wavelengths of NIR light, coupled into tissue via an optical fiber positioned a few centimeters away to collect light and transmit it to a detector. This method has been used extensively to study cerebral oxygenation in the newborn infant (4, 5) (for a review, see (ref. 6)).
Functional Near-Infrared Spectroscopy
During cortical activation, neural excitation produces an increased metabolic demand that results in local changes in oxygen consumption, vasodilatation, increased blood flow, and increased oxygenation. This relationship (...truncated)