Ex-vivo Alzheimer’s disease brain tissue investigation: a multiscale approach using 1060-nm swept source optical coherence tomography for a direct correlation to histology

Abstract. Significance: Amyloid-beta (A-β) plaques are pathological protein deposits formed in the brain of Alzheimer’s disease (AD) patients upon disease progression. Further research is needed to elucidate the complex underlying mechanisms involved in their formation using label-free, tissue preserving, and volumetric techniques. Aim: The aim is to achieve a one-to-one correlation of optical coherence tomography (OCT) data to histological micrographs of brain tissue using 1060-nm swept source OCT. Approach: A-β plaques were investigated in ex-vivo AD brain tissue using OCT with the capability of switching between two magnifications. For the exact correlation to histology, a 3D-printed tool was designed to generate samples with parallel flat surfaces. Large field-of-view (FoV) and sequentially high-resolution volumes at different locations were acquired. The large FoV served to align the OCT to histology images; the high-resolution images were used to visualize fine details. Results: The instrument and the presented method enabled an accurate correlation of histological micrographs with OCT data. A-β plaques were identified as hyperscattering features in both FoV OCT modalities. The plaques identified in volumetric OCT data were in good agreement with immunohistochemically derived micrographs. Conclusion: OCT combined with the 3D-printed tool is a promising approach for label-free, nondestructive, volumetric, and fast tissue analysis.

[1]  M. Villiger,et al.  Label-Free Imaging of Cerebral β-Amyloidosis with Extended-Focus Optical Coherence Microscopy , 2012, The Journal of Neuroscience.

[2]  Marco Augustin,et al.  Assessment of pathological features in Alzheimer’s disease brain tissue with a large field-of-view visible-light optical coherence microscope , 2018, Neurophotonics.

[3]  Brian J. Bacskai,et al.  Label-free imaging of amyloid plaques in Alzheimer’s disease with stimulated Raman scattering microscopy , 2018, Science Advances.

[4]  Junfeng Zhu,et al.  Serial optical coherence scanner for large-scale brain imaging at microscopic resolution , 2014, NeuroImage.

[5]  K. Jellinger,et al.  Alzheimer 100 – highlights in the history of Alzheimer research , 2006, Journal of Neural Transmission.

[6]  Bernhard Baumann,et al.  Optical Coherence Tomography for Brain Imaging , 2019 .

[7]  David A. Boas,et al.  Blockface histology with optical coherence tomography: A comparison with Nissl staining , 2014, NeuroImage.

[8]  Xavier Levecq,et al.  Compact akinetic swept source optical coherence tomography angiography at 1060 nm supporting a wide field of view and adaptive optics imaging modes of the posterior eye , 2018, Biomedical optics express.

[9]  Johannes E. Schindelin,et al.  Fiji: an open-source platform for biological-image analysis , 2012, Nature Methods.

[10]  Christoph K. Hitzenberger,et al.  Comparison of Intensity- and Polarization-based Contrast in Amyloid-beta Plaques as Observed by Optical Coherence Tomography , 2019, Applied Sciences.

[11]  P. Cras,et al.  Senile plaque neurites in Alzheimer disease accumulate amyloid precursor protein. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[12]  G. Glenner,et al.  Morphology and distribution of plaque and related deposits in the brains of Alzheimer's disease and control cases. An immunohistochemical study using amyloid beta-protein antibody. , 1989, Laboratory investigation; a journal of technical methods and pathology.

[13]  J. Hardy,et al.  The amyloid hypothesis of Alzheimer's disease at 25 years , 2016, EMBO molecular medicine.

[14]  Marco Augustin,et al.  Evaluating cellularity and structural connectivity on whole brain slides using a custom-made digital pathology pipeline , 2019, Journal of Neuroscience Methods.

[15]  Shau Poh Chong,et al.  Noninvasive, in vivo imaging of subcortical mouse brain regions with 1.7  μm optical coherence tomography. , 2015, Optics letters.

[16]  S. Gigan,et al.  Brain refractive index measured in vivo with high-NA defocus-corrected full-field OCT and consequences for two-photon microscopy. , 2011, Optics express.

[17]  V. Srinivasan,et al.  Optical coherence microscopy for deep tissue imaging of the cerebral cortex with intrinsic contrast , 2012, Optics express.

[18]  B. Devaux,et al.  Imaging of non-tumorous and tumorous human brain tissues with full-field optical coherence tomography☆ , 2013, NeuroImage: Clinical.

[19]  H. Braak,et al.  [Post-mortem diagnosis of Alzheimer's disease]. , 2005, Der Pathologe.

[20]  Theo Lasser,et al.  Visible spectrum extended-focus optical coherence microscopy for label-free sub-cellular tomography. , 2017, Biomedical optics express.

[21]  B T Hyman,et al.  Growth Arrest of Individual Senile Plaques in a Model of Alzheimer's Disease Observed by In Vivo Multiphoton Microscopy , 2001, The Journal of Neuroscience.

[22]  Marc Dhenain,et al.  Contrast-enhanced MR microscopy of amyloid plaques in five mouse models of amyloidosis and in human Alzheimer’s disease brains , 2017, Scientific Reports.

[23]  P. Thompson,et al.  Brain mapping as a tool to study neurodegeneration , 2007, Neurotherapeutics.

[24]  Benjamin J Vakoc,et al.  Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging , 2009, Nature Medicine.

[25]  Bruce Fischl,et al.  Colocalization of neurons in optical coherence microscopy and Nissl-stained histology in Brodmann’s area 32 and area 21 , 2018, Brain Structure and Function.

[26]  Christoph K. Hitzenberger,et al.  Spectroscopic imaging with spectral domain visible light optical coherence microscopy in Alzheimer’s disease brain samples , 2017, Biomedical optics express.

[27]  Christoph K. Hitzenberger,et al.  Visualization of neuritic plaques in Alzheimer’s disease by polarization-sensitive optical coherence microscopy , 2017, Scientific Reports.

[28]  B. Hyman,et al.  Neuropathological alterations in Alzheimer disease. , 2011, Cold Spring Harbor perspectives in medicine.

[29]  Alzheimer's Association∗.  2019 Alzheimer's disease facts and figures , 2019, Alzheimer's & Dementia.

[30]  Philippe Pouliot,et al.  Whole mouse brain imaging using optical coherence tomography: reconstruction, normalization, segmentation, and comparison with diffusion MRI , 2017, Neurophotonics.

[31]  A. Toga,et al.  Tracking Alzheimer's Disease , 2007, Annals of the New York Academy of Sciences.

[32]  Christoph K. Hitzenberger,et al.  Beyond backscattering: optical neuroimaging by BRAD , 2017, Biomedical optics express.

[33]  K. Scheffler,et al.  Three-dimensional strain fields in human brain resulting from formalin fixation , 2011, Journal of Neuroscience Methods.

[34]  Yongyang Huang,et al.  Optical Coherence Tomography for Brain Imaging and Developmental Biology , 2016, IEEE Journal of Selected Topics in Quantum Electronics.

[35]  Sage C. Arbor,et al.  Amyloid-beta Alzheimer targets — protein processing, lipid rafts, and amyloid-beta pores , 2016, The Yale journal of biology and medicine.