Optical molecular imaging of corpora amylacea in human brain tissue

Label-free multiphoton imaging constitutes a promising technique for clinical diagnosis and therapeutic monitoring. Corpora amylacea (CoA) are starch-like structures often found in the diseased brain, whose origin and role in nervous pathologies are still a matter of debate. Recently, CoA in the diseased human hippocampus were found to be second harmonic generation (SHG) active. Here, we show that CoA formed in other parts of the diseased brain and in brain neoplasms display a similar SHG activity. The SHG pattern of CoA depended on laser polarization, indicating that a radial structure is responsible for their nonlinear activity. Vibrational spectroscopy was used to study the biochemistry underlying the SHG activity. Infrared (IR) and Raman spectroscopy showed that CoA contain polyglucosans that are biochemically similar to glycogen, but with an unusual structure that is similar to amylopectin, which justifies the nonlinear activity of CoA. Our findings explain the SHG activity of CoA and demonstrate that CoA in the pathological brain are amenable to label-free multiphoton imaging. Further research will clarify whether intraoperative assessment of CoA can be diagnostically exploited.