Optical coherence tomography (OCT) reveals depth-resolved dynamics during functional brain activation

Abstract

Optical intrinsic signal imaging (OISI) provides two-dimensional, depth-integrated activation maps of brain activity. Optical coherence tomography (OCT) provides depth-resolved, cross-sectional images of functional brain activation. Co-registered OCT and OISI imaging was performed simultaneously on the rat somatosensory cortex through a thinned skull during forepaw electrical stimulation. Fractional signal change measurements made by OCT revealed a functional signal that correlates well with that of the intrinsic hemodynamic signals and provides depth-resolved, layer-specific dynamics in the functional activation patterns indicating retrograde vessel dilation. OCT is a promising a new technology which provides complementary information to OISI for functional neuroimaging.

Introduction

Optical imaging has become an important technique to investigate the neuronal and vascular responses to brain activation (Orbach et al., 1985, Grinvald et al., 1988, Villringer and Chance, 1997, Gratton and Fabiani, 2001, Franceschini et al., 2006, Hillman, 2007). Optical methods can offer both high spatial and temporal resolutions and are therefore particularly promising for measuring the hemodynamic, metabolic, and neuronal activity in vivo. Optical intrinsic signal imaging (OISI) is a well-established optical imaging method which utilizes a CCD camera to map the clustered activation of neurons. OISI can provide highly sensitive measures of neuronal (Rector et al., 2001, Rector et al., 2005) and vascular (Frostig et al., 1990, Tso et al., 1990) responses to brain activation, and is currently being used extensively for study of the neuro-vascular relationship (Devor et al., 2003, Devor et al., 2005, Sheth et al., 2004, Sheth et al., 2005). However, since CCD cameras integrate the back-scattered light from various depths, OISI cannot detect depth-resolved functional activation. To overcome this limitation, multiphoton microscopy has been used for functional neuronal imaging (Kleinfeld et al., 1998, Bacskai et al., 2003, Chaigneau et al., 2003, Svoboda and Yasuda, 2006). In addition, new methods such as laminar optical tomography (LOT) have been developed for depth-resolved tomographic imaging (Hillman et al., 2004, Hillman et al., 2007). Optical coherence tomography (OCT) is another promising method for depth-resolved imaging in highly scattering tissues such as the cerebral cortex. OCT is an emerging biomedical imaging method which can provide high-resolution, cross-sectional images in vivo and in real time (Huang et al., 1991, Schmitt, 1999). OCT enables the measurement of small, scattered signals over several orders of magnitude in dynamic range and can image deeper than multiphoton microscopy. Several groups have used OCT to study functional activation in neuronal tissues. Maheswari et al. demonstrated depth-resolved, stimulus-specific profiles during functional activation in the cat visual cortex (Maheswari et al., 2002, Maheswari et al., 2003), and showed a good agreement between the depth-integrated functional OCT signals and the OISI profiles (Rajagopalan and Tanifuji, 2007). They attributed these signals to variations in scattering due to localized structural changes such as capillary dilation and cell swelling. Lazebnik et al. (2003) demonstrated scattering changes corresponding to fast and slow signals triggered by action potential propagation in the sea slug abdominal ganglion. Satomura et al. (2004) observed the delayed swelling of the cortical surface in the somatosensory cortex following the electrical stimulation of the rat hind paw. Bizheva et al. (2006) and Srinivasan et al. (2006) reported depth-resolved functional OCT signals in the retina in response to visual stimulation. Recently, Wang et al. (2007) and Wang and Hurst (2007) demonstrated a new Fourier Domain OCT method termed optical angiography (OAG) to visualize the three-dimensional cerebral microcirculation of adult living mice through the intact cranium. Other groups have also explored low coherence interferometry methods for measurement of functional retinal activation (Yao et al., 2005) as well as nerve axon displacement (Akkin et al., 2004, Fang-Yen et al., 2004). In a previous study, we presented preliminary results using OCT to measure subsurface scattering changes due to functional activation in the rat somatosensory cortex (Aguirre et al., 2006). The rat somatosensory cortex is a well-established model system for neurophysiology, and these results demonstrated that OCT can provide high-resolution, cross-sectional measurement of functional hemodynamic response to electrical stimulation in the rat cortex. OCT data correlated well with simultaneously acquired OISI data. This allowed comparison of OCT results with extensively studied intrinsic optical signals. Our previous results suggested that OCT could have an important role in future studies of the functional neurovascular response. In this paper, we perform spatial and temporal correlations of OCT and OISI signals in order to gain further insights for interpretation of OCT results.