The near-infrared autofluorescence fingerprint of the brain

The brain is a vital organ involved in most central nervous system disorders. Their diagnosis and treatment require fast, cost-effective, high-resolution and high-sensitivity imaging. The combination of a new generation of luminescent nanoparticles and imaging systems working in the second biological window (near-infrared II [NIR-II]) is emerging as a reliable alternative. For NIR-II imaging to become a robust technique at the preclinical level, full knowledge of the NIR-II brain autofluorescence, responsible for the loss of image resolution and contrast, is required. This work demonstrates that the brain shows a peculiar infrared autofluorescence spectrum that can be correlated with specific molecular components. The existence of particular structures within the brain with well-defined NIR autofluorescence fingerprints is also evidenced, opening the door to in vivo anatomical imaging. Finally, we propose a rational selection of NIR luminescent probes suitable for low-noise brain imaging based on their spectral overlap with brain autofluorescence.