"The overall goal of OpticMyeliMet project is to develop non-invasive multi-modal non-linear optical (NLO) methods to simultaneously probe myelin and cellular metabolism during the evolution of Multiple sclerosis (MS) pathology. The myelin sheath plays a crucial role in the vertebrate nervous system, by providing energetic support for neurons. MS is characterized by the occurrence of disruption of myelin (demyelination), as well as cellular energetic failure and neurodegeneration. Therefore the development of remyelination strategies remains a crucial therapeutic objective. MS diagnosis and evolution are usually followed by Magnetic Resonance Imaging (MRI), which allows rapid identification of demyelinating MS lesions but with a poor spatial resolution and specificity for single myelin fibers. Potent label-free and non-invasive optical methods to investigate myelin and metabolism pathology and repair at the sub-cellular scale are the key tools for the analysis of demyelinating lesions in MS. OpticMyeliMet project proposes to develop and optimize an ensemble of advanced optical methods to study normal and pathological myelin and cellular redox states in diverse experimental conditions, and to visualize and longitudinally quantify myelin and metabolic states in the brain cortex. Third Harmonic Generation (THG) and Coherent anti-Stokes Raman Scattering (CARS) allow the visualization of myelin sheets without labeling, while two-photon microscopy and Fluorescence Lifetime Microscopy (FLIM) allows the quantification of the intrinsic metabolic coenzyme NADH and the metabolic state of single cells. The project aims to achieve a multi-parametric imaging of myelinated tissues on a ""multiscale"" level, providing an experimental and theoretical framework to relate the imaging data to the myelin organization at the macromolecular (sub-µm) to tissue (tens-to-hundreds of µm) scales."