Laminar optical tomography: high-resolution 3D functional imaging of superficial tissues

Abstract

Laminar Optical Tomography (LOT) is a new medical imaging modality for high-resolution, depth-resolved, functional imaging of superficial tissue such as rodent cortex, skin and the retina. LOT uses visible laser light to image to depths of >2mm (far deeper than microscopy) and is highly sensitive to absorption and fluorescence contrast, enabling spectroscopic functional information such as hemoglobin oxygenation to be imaged with 100-200 micron resolution. LOT has been used to image the hemodynamic response to stimulus in the somatosensory cortex of rats. The resulting three-dimensional (3D) images through the depth of the cortex can be used to delineate the arterial, capillary and venous responses, revealing new information about the intricacies of the oxygenation and blood flow dynamics related to neuronal activation. Additional applications of LOT are being explored, including the integration of 3D Voltage Sensitive Dye fluorescence imaging. LOT imaging uses a system similar to a confocal microscope, quickly scanning a focused beam of light over the surface of the tissue (~8Hz frame rate). Light is detected from both the focus of the scanning beam, and also at increasing distances from the beam's focus. This scattered light has penetrated more deeply into the tissue, and allows features at different depths to be distinguished. An algorithm that includes photon migration modeling of light scattering converts the raw data into 3D images. The motivation for functional optical imaging will be outlined, the basic principles of LOT imaging will be described, and the latest in-vivo results will be presented.