Autor: |
Chang S; Department of Electrical and Computer Engineering, Boston University, 8 St Mary's St, Boston 02215, USA., Yang J; Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston 02215, USA., Novoseltseva A; Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston 02215, USA., Fu X; The Chinese University of Hong Kong, Department of Mechanical Engineering, Hong Kong Special Administrative Region, China., Li C; The Chinese University of Hong Kong, Department of Mechanical Engineering, Hong Kong Special Administrative Region, China., Chen SC; The Chinese University of Hong Kong, Department of Mechanical Engineering, Hong Kong Special Administrative Region, China., Augustinack JC; Department of Radiology, Massachusetts General Hospital, A.A. Martinos Center for Biomedical Imaging, 13th Street, Boston 02129, USA., Magnain C; Department of Radiology, Massachusetts General Hospital, A.A. Martinos Center for Biomedical Imaging, 13th Street, Boston 02129, USA., Fischl B; Department of Radiology, Massachusetts General Hospital, A.A. Martinos Center for Biomedical Imaging, 13th Street, Boston 02129, USA., Mckee AC; VA Boston Healthcare System, U.S. Department of Veteran Affairs.; Boston University Chobanian and Avedisian School of Medicine, Boston University Alzheimer's Disease Research Center and CTE Center.; Department of Neurology, Boston University Chobanian and Avedisian School of Medicine.; Department of Pathology and Laboratory Medicine, Boston University Chobanian and Avedisian School of Medicine.; VA Bedford Healthcare System, U.S. Department of Veteran Affairs, Bedford, MA, USA., Boas DA; Department of Electrical and Computer Engineering, Boston University, 8 St Mary's St, Boston 02215, USA.; Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston 02215, USA., Chen IA; Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston 02215, USA., Wang H; Department of Radiology, Massachusetts General Hospital, A.A. Martinos Center for Biomedical Imaging, 13th Street, Boston 02129, USA. |
Abstrakt: |
The study of neurodegenerative processes in the human brain requires a comprehensive understanding of cytoarchitectonic, myeloarchitectonic, and vascular structures. Recent computational advances have enabled volumetric reconstruction of the human brain using thousands of stained slices, however, tissue distortions and loss resulting from standard histological processing have hindered deformation-free reconstruction of the human brain. The development of a multi-scale and volumetric human brain imaging technique that can measure intact brain structure would be a major technical advance. Here, we describe the development of integrated serial sectioning Polarization Sensitive Optical Coherence Tomography (PSOCT) and Two Photon Microscopy (2PM) to provide label-free multi-contrast imaging, including scattering, birefringence and autofluorescence of human brain tissue. We demonstrate that high-throughput reconstruction of 4×4×2cm 3 sample blocks and simple registration of PSOCT and 2PM images enable comprehensive analysis of myelin content, vascular structure, and cellular information. We show that 2 μm in-plane resolution 2PM images provide microscopic validation and enrichment of the cellular information provided by the PSOCT optical property maps on the same sample, revealing the sophisticated capillary networks and lipofuscin filled cell bodies across the cortical layers. Our method is applicable to the study of a variety of pathological processes, including demyelination, cell loss, and microvascular changes in neurodegenerative diseases such as Alzheimer's disease (AD) and Chronic Traumatic Encephalopathy (CTE). |