Advances in the transport of laser radiation to the brain with optical clearing: From simulation to reality

Advanced laser methods have recently been used in human and animal head tissues for functional and molecular imaging. Combining these approaches with various probes and nanostructures gives up a new path for theranostic applications in brain tissues. The diverse optical properties of head tissues such as the scalp, skull, cerebrospinal fluid, and brain tissues result in considerable photon scattering and absorption. Diffusion of photons inside head tissues decreases the optical imaging quality and limits the optical resolutions of cellular and neural treatments. Tissue optical clearing (TOC) was set up more than a century ago to make tissue transparent by immersing it in liquids with a matching RI as the tissue. This approach has lately gained popularity in the field of brain imaging. The physical fundamentals of optical clearing (OC) procedures for brain tissue, such as RI matching with chemical agents, dehydration, delipidation, decalcification, hyperhydration, and innovative hybrid brain OC methods, are explored here. This study covers critical issues such as choosing the best brain OC methods and optimizing wavelength and laser energy to control tissue optical properties. Here, innovative ways for decreasing photon scattering based on immersion procedures and induced heating tunnels are discussed. In addition, simulation methods of photon migration in brain tissues (based on random approaches) are investigated, paving the way for the proper brain OC strategy. Finally, the limitations of this method for in vivo applications are discussed, as well as possible applications in cranial implants, optogenetics, laser brain stimulation, and functional optical imaging.