Brain imaging and mapping with multi-contrast optical coherence tomography

The brain is a highly heterogeneous network with billions of neurons communicating through trillions of synaptic connections. In the past decades, system-level imaging techniques such as functional MRI and PET and high-resolution microscopes have revolutionized our understanding of regional activity and single-neuron functions. However, our knowledge of how these neurons are coordinated to form complex behaviors and what go wrong under neurological disorders are yet sparsely scattered, without coherently linked apprehension. The questions need to be addressed in all aspects: the cell types and neuronal connections in the network, the dynamic circuitry and chemicals under neural activity, and the supporting systems such as blood supply and microenvironment. Systematic explorations of these subjects have imposed a pressing need for innovative neuroimaging techniques that simultaneously possess the power of high spatiotemporal resolution and considerable coverage of the brain. The emergence of optical coherence tomography (OCT) (Huang et al., 1991) offers a viable solution for 3D reconstruction of biological tissues with high spatiotemporal resolution. OCT, analogous to ultrasound imaging, makes use of an optical interferometry to provide cross-sectional and 3D images of tissue microstructures up to a few millimeters of depth. The signal is intrinsically originated from the light backscattered from the sample, thus enabling noninvasive or minimally invasive in vivo studies. Since its invention, OCT has proved to be an appealing tool in a wide range of applications in neuroscience (Boppart, 2003). The technique has been extensively established in the application of ophthalmology, especially the retina, for a variety of purposes. Its ability to quantitatively examine the multiple neuronal layers in the retina and the associated fner structures has provided an easily accessible window for studying central nervous system diseases, such as multiple sclerosis (Frohman et al., 2008). Feasibility of OCT in localizing nerves and blood vessels has been investigated in rabbit (Boppart et al., 1998a). In the functional studies of neural activity, the intensity and phase changes of OCT signals without and with voltage-sensitive dyes have been correlated with changes of membrane potentials in isolated nerve (Akkin et al., 2010). The brain consists of hundreds of neuronal types with a diversity of morphology and shapes (Bertrand et al., 2002). The interpretation of the intricate organizations and connections could be confounded on 2D microscopy images. The 3D imaging in OCT restores the compressed space to its full visibility. It is essentially important in revealing delicate features and complex architectures in brain with high resolution (2-20 um) and remarkable sensitivity (~100 dB). The imaging depth allows for whole-brain imaging in semitransparent animal models, such as Xenopus and zebra fsh, in the developmental stage (Boppart et al., 1996a, b). In mammal brains, the imaging depth of ~1 mm has been found in the cerebral cortex (Jeon et al., 2006), which is suffcient for studying intact cerebral laminar structures and functions in small animals such as mouse and rat. Although deep brain imaging is limited by light attenuation due to scattering and absorption events, reconstruction of the whole-brain space is possible ex vivo by fusing volumetric data from sequential OCT scans (Wang et al., 2014a). OCT signal comes from the inherent optical property of tissues without the need of exogenous contrast agents. Besides the conventional OCT, there are specialized OCT techniques. These include polarization-sensitive OCT (De Boer et al., 1997), Doppler OCT (Chen et al., 1997), and optical microangiography (Makita et al., 2006; Wang et al., 2007), which are capable of probing white matter tracts, cerebral blood circulation, and microvasculature networks, respectively, in brain studies. OCT rigs that incorporate multiple specializations into one single system are called multi-contrast (MC) OCT herein. The MC-OCT enables simultaneous imaging of several contrasts in one scan. This integration has several advantages. From the spatial perspective, it allows for the interrogation of structural architectures probed by different contrasts through automatically aligned framework. From the temporal perspective, it provides the interaction of different signals revealing physiological processes through simultaneous data collection. The merits are particularly benefcial in answering important neuroscience questions such as neurovascular coupling, brain mapping, and brain-wide wiring diagram, and their topological relationship with cell types. In this chapter, we review the basics of OCT techniques and the structural brain imaging and mapping studies using multiple OCT contrasts.