期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：48
DOI：10.1073/pnas.2113835118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
We demonstrate multiscale phase-contrast X-ray computed tomography (CT) of postmortem human brain tissue. Large tissue volumes can be covered by parallel-beam CT and combined with subcellular detail for selected regions scanned at high magnification. This has been repeated identically for a larger number of individuals, including both Alzheimer’s-diseased patients and a control group. Optimized phase retrieval, followed by automated segmentation based on machine learning, as well as feature identification and classification based on optimal transport theory, indicates a pathway from healthy to pathological structure without prior hypothesis. This study provides a blueprint for studying the cytoarchitecture of the human brain and its alterations associated with neurodegenerative diseases.
We have studied the three-dimensional (3D) cytoarchitecture of the human hippocampus in neuropathologically healthy and Alzheimer’s disease (AD) individuals, based on phase-contrast X-ray computed tomography of postmortem human tissue punch biopsies. In view of recent findings suggesting a nuclear origin of AD, we target in particular the nuclear structure of the dentate gyrus (DG) granule cells. Tissue samples of 20 individuals were scanned and evaluated using a highly automated approach of measurement and analysis, combining multiscale recordings, optimized phase retrieval, segmentation by machine learning, representation of structural properties in a feature space, and classification based on the theory of optimal transport. Accordingly, we find that the prototypical transformation between a structure representing healthy granule cells and the pathological state involves a decrease in the volume of granule cell nuclei, as well as an increase in the electron density and its spatial heterogeneity. The latter can be explained by a higher ratio of heterochromatin to euchromatin. Similarly, many other structural properties can be derived from the data, reflecting both the natural polydispersity of the hippocampal cytoarchitecture between different individuals in the physiological context and the structural effects associated with AD pathology.
关键词：X-ray phase-contrast tomography; multiscale imaging; human hippocampus; 3D virtual histology; Alzheimer’s disease
