Autofluorescence spectroscopy as a proxy for chronic white matter pathology

Background: The balance of tissue injury and repair ultimately determines outcomes of chronic neurological disorders, such as progressive multiple sclerosis (MS). However, the extent of pathology can be difficult to detect, particularly when it is insidious and/or offset by tissue regeneration. Objectives: The objective of this research is to evaluate whether tissue autofluorescence—typically a source of contamination—provides a surrogate marker of white matter injury. Methods: Tissue autofluorescence in autopsied specimens both experimental and clinical was characterized by spectral confocal microscopy and correlated to severity and chronicity as determined by standard histopathology. Results: Months after cuprizone (CPZ)-induced demyelination, despite robust remyelination, autofluorescent deposits progressively accumulated in regions of prior pathology. Autofluorescent deposits (likely reflecting myelin debris remnants) were conspicuously localized to white matter, proportional to lesion severity, and displayed differential fluorescence over time. Strikingly, similar features were apparent also in autopsied MS tissue. Conclusion: Autofluorescence spectroscopy illuminates prior and ongoing white matter injury. The accumulation of autofluorescence in proportion to the extent of progressive atrophy, despite robust remyelination in the CPZ brain, provides important proof-of-concept of a phenomenon (insidious ongoing damage masked by mechanisms of tissue repair) that we hypothesize is highly relevant to the progressive phase of MS.