Imaging brain function with optical topography

For more than two decades, the single channel measurement technique of NIR spectroscopy (NIRS) has been successfully used to measure the haemodynamic response to brain activity in both adults and neonates (Hoshi 2003). It has been used to record functional activity for research into brain cognition, and to examine brain development in infants (Obrig and Villringer 2003). An obvious limitation of NIRS is the lack of any spatial information. It is natural to consider combining multiple NIRS measurements in order to localise the origin of signals in the brain; indeed, the first optical topography studies were carried out in this way (Maki et al. 1995, Gratton et al. 1995).

NIRS and optical topography measure the haemodynamic response following brain activation and therefore rely on the spatial and temporal variability in the concentration and oxygenation of haemoglobin in the blood. The penetration depth of optical topographic systems is generally assumed to be approximately half the optode spacing. For typical spacings around 25-35 mm, this gives a penetration depth of about 15 mm, which is sufficient for sampling the adult cortex. Recent reviews of optical topography have been provided by Strangman et al. (2002), Hebden (2003) and Koizumi et al. (2003).

The most commonly used method for imaging brain function is functional MRI, which is sensitive to the Blood Oxygen Level Dependent (BOLD) signal. BOLD MRI detects signal changes caused by the magnetic susceptibility of deoxyhemoglobin (HHb) being greater than that of oxyhemoglobin (HbO) and other brain tissues, and generates images of these changes in a few seconds. It is currently viewed as the Gold Standard for functional brain imaging due partly to the ability to register fMRI images directly onto a structural MR image taken during the same examination. However, optical topography does have some advantages over fMRI which have led to it developing an increasing role in functional brain imaging. For example, images can be acquired very rapidly (a 50 Hz acquisition rate has been demonstrated by Franceschini et al. (2003)), and it is inexpensive and portable, enabling images to be obtained at the bedside or in the laboratory. Moreover, mechanisms which generate the NIRS signal are closely correlated with the BOLD signal of fMRI but add information by distinguishing quantitatively between changes in [HHb] and [HbO] (Strangman et al. 2002b). The primary drawback of optical imaging is the inherently low spatial resolution, which is about 10 mm at best. However, although the spatial resolution of fMRI is typically 3 mm and can be as good as 1 mm, the image processing techniques which are commonly used model the image as a smoothed random field and so impose a smoothing filter with a 8-10 mm Gaussian kernel before analysis (Turner and Jones 2003). In certain circumstances, therefore, there may be little difference between the effective spatial resolutions of the two techniques.

Optical topography of the adult brain has been largely pioneered by researchers from the Hitachi Medical Corporation (Tokyo, Japan), who have used the ETG-100 Optical Topography System (Figure 3), described in section 2.2, to examine a range of cognitive tasks (Takahashi et al. 2000, Koizumi et al. 2003). Optical methods are well suited for imaging tasks related to language, as the investigation is silent, unlike fMRI (Watanabe et al. 1998). Optical topography is beginning to be routinely applied to pathological conditions: Watanabe et al. (1998, 2002) showed that optical topography could detect changes in [HbO] and [HHb] during epileptic seizures, and Matsuo et al. (2003) showed a difference in the response to viewing traumatic images between normal controls and patients who suffered post traumatic stress disorder from the 1995 sarin nerve gas attack on the Tokyo subway. Meanwhile, Obata et al. (2003) showed that visual evoked responses were not affected by alcohol.

Franceschini et al. (2003) have used a related approach to image the sensorimotor cortex using a system with 8 laser diode sources at each of two wavelengths and 16 detectors. Each channel was frequency-encoded, allowing all the sources and detectors to be active simultaneously and decoded in software to maximise the image acquisition rate. Using this method, images could be obtained at 50 Hz. They found an increase in [HbO] and a decrease in [HHb] contralateral to the stimulated side with a reduced ipsilateral response, consistent with equivalent fMRI and PET studies.

The Hitachi approach generates images by assuming that a change in intensity originates midway between the source and detector which measured that change. The image is produced by mapping the changes according to the positions of the appropriate source-detector pair. This technique has some drawbacks: the spatial resolution cannot be better than the optode spacing, it is difficult to apply it to irregular arrangements of connectors, and it does not naturally allow the inclusion of prior information (Yamamoto et al. 2002). These limitations have been addressed by (Boas et al. 2001) who showed that a linear reconstruction approach improves the quantitative accuracy compared to single channel NIRS measurements (and, by implication, images generated by mapping, which are equivalent to multiple NIRS measurements). Furthermore, such an approach allows multiple topographic measurements to contribute to each pixel, which can yield a two-fold improvement in spatial resolution and localisation accuracy (Boas et al. 2004). Culver et al. (2003) have used a similar approach based on linear reconstruction to image the rat cortex.

Most optical topographic images have been obtained using systems which measure intensity alone, meaning that the effects of µa and µ's cannot be uniquely separated (Arridge and Lionheart 1998). This has been addressed by Franceschini et al. (2000) who used a frequency-domain system to acquire images of activity in the adult cortex with a time resolution of 160 ms. The system uses 8 sources at each of two wavelengths (758 and 830 nm) and two detectors, and is produced commercially by ISS Inc, USA. (Toronov et al. 2001a) used a similar system to record optical data during motor activity simultaneously with fMRI images. They found close spatial and temporal agreement between the optical and BOLD signals. In a related study, Toronov et al. (2001) showed that both the amplitude and the phase of the NIRS signal correlated with the BOLD response.

Optical imaging techniques are particularly well suited to imaging infants, being portable and somewhat less sensitive to motion artefact than fMRI. The first report of optical topography on premature babies was by Chance et al. (1998) who used a system with 9 sources and 4 detectors on adults and on a 4-week old neonate. The system measured intensity only but used a phase cancellation technique to improve sensitivity. Sources were arranged on a grid and a signal applied to alternate sources at phase shifts of either 0 degrees or 180 degrees such that, in a homogeneous medium, the phase shift is 90 degrees and the amplitude is zero directly between the sources, where the detectors are placed. The Hitachi systems have also been used to investigate brain activity in infants. Taga et al. (2000) observed spontaneous fluctuations in [HHb] and [HbO] in eight sleeping neonates with periods of 8-11 s which were attributed to vasomotion. Oscillations in [HHb] led those in [HbO] by 3?/4, which was explained by a localised increase in brain activity leading to an increase in [HHb], followed by an increase in cerebral blood flow which supplies additional oxygen to increase [HbO]. A similar effect has been observed in BOLD fMRI. More recently, the same group examined 20 infants a few months old and were able to record images during visual activation from eight infants (Taga et al. 2003). The other 12 were rejected due to movement, crying, lack of attention and poor contact due to hair. They concluded that the convenience of optical topography represented a significant advantage over other techniques. Kusaka et al. (2004) carried out a similar study using a CW system supplied by Shimadzu Corporation and showed different responses between adults and infants. Higher cognitive functions have also been imaged using the Hitachi system - Peña et al. (2003) showed that the temporal cortex in neonates is activated more strongly by normal speech than by speech played backwards, and Tsujimoto et al. (2004) showed that the same area of the brain, the lateral prefrontal cortex, appears to be responsible for working memory in both adults and pre-school children. Both of the latter two articles comment on the convenience with which optical topography can be used to image babies and children. Vaithianathan et al. (2004) has built and tested a CW topography system with an interface consisting of a flexible pad, designed to be conveniently applied to an infants head.

Hintz et al. (2001) used a CW topography system to image passive motor activity in premature infants. Their system acquires a total of 144 independent measurements in approximately 3 s, and images were reconstructed using a non-linear approach. Bluestone et al. (2001) used an even more sophisticated image reconstruction technique to generate 3D images of a region of interest beneath the adult forehead during a Valsalva manoeuvre, in which the intrathoracic pressure is increased (and therefore cardiac output decreased) by expiration against a closed airway. They used a CW system (Schmitz et al. 2002) to acquire data from 15 optodes on the forehead with a temporal resolution of 3 Hz.

Optical topography has been extensively used to image functional brain activity in both adults and neonates. During the past five years it has evolved beyond a laboratory technique to be used to address hypothesis-led questions about neurophysiology and brain development. It has unique advantages over other brain imaging techniques, including its excellent temporal resolution and its ability to distinguish between [HHb] and [HbO]. It can be used in a natural, relaxed environment, making it well suited for psychological studies, and it can be used to image awake infants.