Tissue optical clearing for 3D visualization of vascular networks: A review

Reconstruction of the vasculature of intact tissues/organs down to the capillary level is essential for understanding the development and remodeling of vascular networks under physiological and pathological conditions. Optical imaging techniques can provide sufficient resolution to distinguish small vessels with several microns, but the imaging depth is somewhat limited due to the high light scattering of opaque tissue. Recently, various tissue optical clearing methods have been developed to overcome light attenuation and improve the imaging depth both for ex-vivo and in-vivo visualizations. Tissue clearing combined with vessel labeling techniques and advanced optical tomography enables successful mapping of the vasculature of different tissues/organs, as well as dynamically monitoring vessel function under normal and pathological conditions. Here, we briefly introduce the commonly-used labeling strategies for entire vascular networks, the current tissue optical clearing techniques available for various tissues, as well as the advanced optical imaging techniques for fast, high-resolution structural and functional imaging for blood vessels. We also discuss the applications of these techniques in the 3D visualization of vascular networks in normal tissues, and the vascular remodeling in several typical pathological models in clinical research. This review is expected to provide valuable insights for researchers to study the potential mechanisms of various vessel-associated diseases using tissue optical clearing pipeline.