A cellular resolution atlas of Broca’s area

Author:

Costantini Irene123ORCID,Morgan Leah4ORCID,Yang Jiarui5,Balbastre Yael46ORCID,Varadarajan Divya46ORCID,Pesce Luca1ORCID,Scardigli Marina178ORCID,Mazzamuto Giacomo137ORCID,Gavryusev Vladislav17ORCID,Castelli Filippo Maria179ORCID,Roffilli Matteo9ORCID,Silvestri Ludovico137ORCID,Laffey Jessie10ORCID,Raia Sophia10ORCID,Varghese Merina10ORCID,Wicinski Bridget10,Chang Shuaibin11ORCID,Chen Ichun Anderson5,Wang Hui46ORCID,Cordero Devani4ORCID,Vera Matthew4ORCID,Nolan Jackson4ORCID,Nestor Kimberly46ORCID,Mora Jocelyn46ORCID,Iglesias Juan Eugenio461213ORCID,Garcia Pallares Erendira4ORCID,Evancic Kathryn46,Augustinack Jean C.46ORCID,Fogarty Morgan1415ORCID,Dalca Adrian V.413ORCID,Frosch Matthew P.16ORCID,Magnain Caroline46ORCID,Frost Robert46ORCID,van der Kouwe Andre4617,Chen Shih-Chi18ORCID,Boas David A.5ORCID,Pavone Francesco Saverio137,Fischl Bruce461319ORCID,Hof Patrick R.10ORCID

Affiliation:

1. European Laboratory for Non-Linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino (FI), Italy.

2. Department of Biology, University of Florence, Florence, Italy.

3. National Institute of Optics (INO), National Research Council (CNR), Sesto Fiorentino, Italy.

4. Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.

5. Department of Biomedical Engineering, Boston University, Boston, MA, USA.

6. Department of Radiology, Harvard Medical School, Boston, MA, USA.

7. Department of Physics and Astronomy, University of Florence, Sesto Fiorentino (FI), Italy.

8. Division of Physiology, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.

9. Bioretics srl, Cesena, Italy.

10. Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

11. Department of Electrical and Computer Engineering, Boston University, Boston, MA, USA.

12. Department of Medical Physics and Biomedical Engineering, University College London, London, UK.

13. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA.

14. Imaging Science Program, Washington University McKelvey School of Engineering, St. Louis, MO, USA.

15. Department of Radiology, Washington University School of Medicine, St. Louis, MO, USA.

16. C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

17. Department of Human Biology, University of Cape Town, Cape Town, South Africa.

18. Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Shatin, Hong Kong.

19. HST, Massachusetts Institute of Technology, Cambridge, MA, USA.

Abstract

Brain cells are arranged in laminar, nuclear, or columnar structures, spanning a range of scales. Here, we construct a reliable cell census in the frontal lobe of human cerebral cortex at micrometer resolution in a magnetic resonance imaging (MRI)–referenced system using innovative imaging and analysis methodologies. MRI establishes a macroscopic reference coordinate system of laminar and cytoarchitectural boundaries. Cell counting is obtained with a digital stereological approach on the 3D reconstruction at cellular resolution from a custom-made inverted confocal light-sheet fluorescence microscope (LSFM). Mesoscale optical coherence tomography enables the registration of the distorted histological cell typing obtained with LSFM to the MRI-based atlas coordinate system. The outcome is an integrated high-resolution cellular census of Broca’s area in a human postmortem specimen, within a whole-brain reference space atlas.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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