Organs such as the heart and brain possess intricate fiber structures that are best characterized with three-dimensional imaging. For instance, diffusion-based, magnetic resonance tractography (MRT) enables studies of connectivity and remodeling during development and disease macroscopically on the millimeter scale. Here we present complementary, high-resolution microscopic optical coherence imaging and analysis methods that, when used in conjunction with clearing techniques, can characterize fiber architecture in intact organs at tissue depths exceeding 1 mm. We anticipate that these techniques can be used to study fiber architecture in situ at microscopic scales not currently accessible to diffusion magentic resonance (MR), and thus, to validate and complement macroscopic structural imaging techniques. Moreover, as these techniques use intrinsic signals and do not require tissue slicing and staining, they can be used for high-throughput, nondestructive evaluation of fiber architecture across large tissue volumes.
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