title: Visualization of neuritic plaques in Alzheimer's disease by polarization-sensitive optical coherence microscopy.
abstract: One major hallmark of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) is the deposition of extracellular senile plaques and vessel wall deposits composed of amyloid-beta (Aβ). In AD, degeneration of neurons is preceded by the formation of Aβ plaques, which show different morphological forms. Most of them are birefringent owing to the parallel arrangement of amyloid fibrils. Here, we present polarization sensitive optical coherence microscopy (PS-OCM) for imaging mature neuritic Aβ plaques based on their birefringent properties. Formalin-fixed, post-mortem brain samples of advanced stage AD patients were investigated. In several cortical brain regions, neuritic Aβ plaques were successfully visualized in tomographic and three-dimensional (3D) images. Cortical grey matter appeared polarization preserving, whereas neuritic plaques caused increased phase retardation. Consistent with the results from PS-OCM imaging, the 3D structure of senile Aβ plaques was computationally modelled for different illumination settings and plaque sizes. Furthermore, the birefringent properties of cortical and meningeal vessel walls in CAA were investigated in selected samples. Significantly increased birefringence was found in smaller vessels. Overall, these results provide evidence that PS-OCM is able to assess amyloidosis based on intrinsic birefringent properties.
authors.affiliation: Medical University of Vienna, Center for Medical Physics and Biomedical Engineering, A-1090, Vienna, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Baumann
authors.affiliation: General Hospital and Medical University of Vienna, Institute of Neurology, A-1090, Vienna, Austria.
authors.forename: Adelheid
authors.initials: A
authors.lastname: Woehrer
authors.affiliation: General Hospital and Medical University of Vienna, Institute of Neurology, A-1090, Vienna, Austria.
authors.forename: Gerda
authors.initials: G
authors.lastname: Ricken
authors.affiliation: Medical University of Vienna, Center for Medical Physics and Biomedical Engineering, A-1090, Vienna, Austria.
authors.forename: Marco
authors.initials: M
authors.lastname: Augustin
authors.affiliation: General Hospital and Medical University of Vienna, Institute of Neurology, A-1090, Vienna, Austria.|General Hospital and Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, A-1090, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Mitter
authors.affiliation: Medical University of Vienna, Center for Medical Physics and Biomedical Engineering, A-1090, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Pircher
authors.affiliation: General Hospital and Medical University of Vienna, Institute of Neurology, A-1090, Vienna, Austria.
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Kovacs
authors.affiliation: Medical University of Vienna, Center for Medical Physics and Biomedical Engineering, A-1090, Vienna, Austria.
authors.forename: Christoph K
authors.initials: CK
authors.lastname: Hitzenberger
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology; D001344:Autopsy; D001718:Birefringence; D016657:Cerebral Amyloid Angiopathy / Q000000981:diagnostic imaging* / Q000473:pathology; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000473:pathology / Q000648:ultrastructure; D005454:Fluorescence Polarization; D005557:Formaldehyde; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000706:statistics & numerical data; D008578:Meninges / Q000000981:diagnostic imaging* / Q000473:pathology / Q000648:ultrastructure; D008859:Microscopy, Polarization / Q000295:instrumentation / Q000379:methods*; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000473:pathology / Q000648:ultrastructure; D016707:Tissue Fixation / Q000379:methods; D041623:Tomography, Optical Coherence / Q000295:instrumentation / Q000379:methods*
chemical_list: D005557:Formaldehyde