Cellular 3D-reconstruction and analysis in the human cerebral cortex using automatic serial sections

Nick Y Larsen; Xixia Li; Xueke Tan; Gang Ji; Jing Lin; Grazyna Rajkowska; Jesper Møller; Ninna Vihrs; Jon Sporring; Fei Sun; Jens R Nyengaard

doi:10.1038/s42003-021-02548-6

Cellular 3D-reconstruction and analysis in the human cerebral cortex using automatic serial sections

Commun Biol. 2021 Sep 2;4(1):1030. doi: 10.1038/s42003-021-02548-6.

Authors

Nick Y Larsen^{1

2

3

4}, Xixia Li^{5

6}, Xueke Tan^{5

6}, Gang Ji^{5

6}, Jing Lin⁷, Grazyna Rajkowska⁸, Jesper Møller^{9

10}, Ninna Vihrs¹⁰, Jon Sporring^{9

7}, Fei Sun^#^{11

12

5

6}, Jens R Nyengaard^#^{13

9

11

14}

Affiliations

¹ Core Centre for Molecular Morphology, Section for Stereology and Microscopy, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. nylarsen@clin.au.dk.
² Centre for Stochastic Geometry and Advanced Bioimaging, Aalborg University, Aarhus University and University of Copenhagen, Aalborg, Aarhus and Copenhagen, Denmark. nylarsen@clin.au.dk.
³ Sino-Danish Center for Education and Research, Aarhus, Denmark. nylarsen@clin.au.dk.
⁴ University of the Chinese Academy of Sciences, Beijing, China. nylarsen@clin.au.dk.
⁵ National Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
⁶ Center for Biological Imaging, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
⁷ Department of Computer Science, University of Copenhagen, Copenhagen, Denmark.
⁸ Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA.
⁹ Centre for Stochastic Geometry and Advanced Bioimaging, Aalborg University, Aarhus University and University of Copenhagen, Aalborg, Aarhus and Copenhagen, Denmark.
¹⁰ Department of Mathematical Sciences, Aalborg University, Aalborg, Denmark.
¹¹ Sino-Danish Center for Education and Research, Aarhus, Denmark.
¹² University of the Chinese Academy of Sciences, Beijing, China.
¹³ Core Centre for Molecular Morphology, Section for Stereology and Microscopy, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
¹⁴ Department of Pathology, Aarhus University, Aarhus, Denmark.

^# Contributed equally.

Abstract

Techniques involving three-dimensional (3D) tissue structure reconstruction and analysis provide a better understanding of changes in molecules and function. We have developed AutoCUTS-LM, an automated system that allows the latest advances in 3D tissue reconstruction and cellular analysis developments using light microscopy on various tissues, including archived tissue. The workflow in this paper involved advanced tissue sampling methods of the human cerebral cortex, an automated serial section collection system, digital tissue library, cell detection using convolution neural network, 3D cell reconstruction, and advanced analysis. Our results demonstrated the detailed structure of pyramidal cells (number, volume, diameter, sphericity and orientation) and their 3D spatial organization are arranged in a columnar structure. The pipeline of these combined techniques provides a detailed analysis of tissues and cells in biology and pathology.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cerebral Cortex / anatomy & histology*
Humans
Imaging, Three-Dimensional / methods*
Microscopy
Microscopy, Electron
Microtomy*

Grants and funding

P30 GM103328/GM/NIGMS NIH HHS/United States