Assessment of pathological features in Alzheimer’s disease brain tissue with a large field-of-view visible-light optical coherence microscope

Abstract

. We implemented a wide field-of-view visible-light optical coherence microscope (OCM) for investigating ex-vivo brain tissue of patients diagnosed with Alzheimer’s disease (AD) and of a mouse model of AD. A submicrometer axial resolution in tissue was achieved using a broad visible light spectrum. The use of various objective lenses enabled reaching micrometer transversal resolution and the acquisition of images of microscopic brain features, such as cell structures, vessels, and white matter tracts. Amyloid-beta plaques in the range of 10 to were visualized. Large field-of-view images of young and old mouse brain sections were imaged using an automated stage. The plaque load was characterized, revealing an age-related increase. Human brain tissue affected by cerebral amyloid angiopathy was investigated and hyperscattering structures resembling amyloid beta accumulations in the vessel walls were identified. All results were in good agreement with histology. A comparison of plaque features in both human and mouse brain tissue was performed, revealing an increase in plaque load and a decrease in reflectivity for mouse as compared with human brain tissue. Based on the promising outcome of our experiments, visible light OCM might be a powerful tool for investigating microscopic features in ex-vivo brain tissue.

Comparison of Intensity- and Polarization-based Contrast in Amyloid-beta Plaques as Observed by Optical Coherence Tomography

“…PS-OCT visualizes amyloid-beta plaques based on their optical scattering and birefringent properties [33][34][35][36]. Previous studies mainly exploited the hyperscattering characteristics of plaques and only one report investigated the birefringent characteristics of neuritic plaques using PS-OCT [19].…”

“…Several recent reports have demonstrated that amyloid-beta plaques in both human and mouse brain tissue can be visualized using either conventional OCT, PS-OCT [19,[32][33][34][35][36] or other functional extensions such as spectroscopic OCT [32] or directional OCT [36]. Label-free imaging of cerebral amyloid-beta plaques has been achieved using extended-focus optical coherence microscopy (OCM) in the near infrared range at 800 nm [34].…”

“…These measurements provided information about the polarization characteristics of these pathological structures [19]. Finally, a spectral-domain visible light OCM system with sub-micrometer axial resolution has been used to investigate the inherent scattering contrast and the spectroscopic properties of amyloid-beta plaques in ex-vivo human and mouse brain tissue [32,33]. To the best of our knowledge, no previous study has evaluated the capabilities of OCT and PS-OCT for amyloid-beta imaging in a large human sample cohort.…”

Advances in Ex Situ Tissue Optical Clearing

“…Such evaluations along with spectroscopic studies might help elucidate the most optimal clearing conditions/formulas for particular organs of interest . Optical coherence microscopy coupled with CLARITY‐processed brain facilitated detection of Congo red–stained amyloid‐beta plaques in an animal model of Alzheimer's disease . Interestingly, only one day of optical clearing doubled the penetration depth (100 µm vs 200 µm, Figure ).…”

“…b–d) 2 days of SWITCH brain clearing doubles imaging depth (b) and decreases both mean OCM amplitude (c) and mean global attenuation (d) as normalized to noncleared tissue (shaded bands represent standard deviations). a) Reproduced under the terms of the CC‐BY Creative Commons Attribution 3.0 Unported license ( https://creativecommons.org/licenses/by/3.0/) . Copyright 2018, The Authors.…”