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A multimodal imaging and analysis pipeline for creating a cellular census of the human cerebral cortex

View ORCID ProfileIrene Costantini, Leah Morgan, Jiarui Yang, Yael Balbastre, Divya Varadarajan, Luca Pesce, Marina Scardigli, Giacomo Mazzamuto, Vladislav Gavryusev, Filippo Maria Castelli, Matteo Roffilli, Ludovico Silvestri, Jessie Laffey, Sophia Raia, Merina Varghese, Bridget Wicinski, Shuaibin Chang, Anderson Chen I-Chun, Hui Wang, Devani Cordero, Matthew Vera, Jackson Nolan, Kim Nestor, Jocelyn Mora, Juan Eugenio Iglesias, Erendira Garcia Pallares, Kathryn Evancic, Jean Augustinack, Morgan Fogarty, Adrian V. Dalca, Matthew Frosch, Caroline Magnain, Robert Frost, Andre van der Kouwe, Shih-Chi Chen, David A. Boas, Francesco Saverio Pavone, Bruce Fischl, Patrick R. Hof
doi: https://doi.org/10.1101/2021.10.20.464979
Irene Costantini
1European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino (FI), Italy
2Department of Biology, University of Florence, Italy
3National Institute of Optics (INO), National Research Council (CNR), Italy
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  • ORCID record for Irene Costantini
  • For correspondence: costantini@lens.unifi.it
Leah Morgan
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
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Jiarui Yang
6Boston University, Department of Biomedical Engineering, Boston, USA
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Yael Balbastre
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
5Department of Radiology, Harvard Medical School, Boston, MA, USA
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Divya Varadarajan
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
5Department of Radiology, Harvard Medical School, Boston, MA, USA
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Luca Pesce
1European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino (FI), Italy
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Marina Scardigli
1European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino (FI), Italy
7Department of Physics and Astronomy, University of Florence, Sesto Fiorentino (FI), Italy
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Giacomo Mazzamuto
1European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino (FI), Italy
3National Institute of Optics (INO), National Research Council (CNR), Italy
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Vladislav Gavryusev
1European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino (FI), Italy
7Department of Physics and Astronomy, University of Florence, Sesto Fiorentino (FI), Italy
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Filippo Maria Castelli
1European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino (FI), Italy
7Department of Physics and Astronomy, University of Florence, Sesto Fiorentino (FI), Italy
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Matteo Roffilli
8Bioretics srl, Cesena, Italy
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Ludovico Silvestri
1European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino (FI), Italy
3National Institute of Optics (INO), National Research Council (CNR), Italy
7Department of Physics and Astronomy, University of Florence, Sesto Fiorentino (FI), Italy
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Jessie Laffey
9Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Sophia Raia
9Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Merina Varghese
9Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Bridget Wicinski
9Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Shuaibin Chang
10Boston University, Department of Electrical and Computer Engineering, Boston, USA
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Anderson Chen I-Chun
6Boston University, Department of Biomedical Engineering, Boston, USA
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Hui Wang
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
5Department of Radiology, Harvard Medical School, Boston, MA, USA
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Devani Cordero
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
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Matthew Vera
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
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Jackson Nolan
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
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Kim Nestor
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
5Department of Radiology, Harvard Medical School, Boston, MA, USA
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Jocelyn Mora
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
5Department of Radiology, Harvard Medical School, Boston, MA, USA
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Juan Eugenio Iglesias
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
5Department of Radiology, Harvard Medical School, Boston, MA, USA
11Department of Medical Physics and Biomedical Engineering, University College London, London, UK
12Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA
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Erendira Garcia Pallares
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
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Kathryn Evancic
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
5Department of Radiology, Harvard Medical School, Boston, MA, USA
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Jean Augustinack
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
5Department of Radiology, Harvard Medical School, Boston, MA, USA
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Morgan Fogarty
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
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Adrian V. Dalca
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
12Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA
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Matthew Frosch
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
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Caroline Magnain
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
5Department of Radiology, Harvard Medical School, Boston, MA, USA
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Robert Frost
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
5Department of Radiology, Harvard Medical School, Boston, MA, USA
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Andre van der Kouwe
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
5Department of Radiology, Harvard Medical School, Boston, MA, USA
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Shih-Chi Chen
13The Chinese University of Hong Kong, Department of Mechanical Engineering, Hong Kong Special Administrative Region, China
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David A. Boas
6Boston University, Department of Biomedical Engineering, Boston, USA
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Francesco Saverio Pavone
1European Laboratory for Non-linear Spectroscopy (LENS), University of Florence, Sesto Fiorentino (FI), Italy
3National Institute of Optics (INO), National Research Council (CNR), Italy
7Department of Physics and Astronomy, University of Florence, Sesto Fiorentino (FI), Italy
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Bruce Fischl
4Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA
5Department of Radiology, Harvard Medical School, Boston, MA, USA
12Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA
14HST, Massachusetts Institute of Technology, Cambridge, MA, USA
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Patrick R. Hof
9Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Abstract

Cells are not uniformly distributed in the human cerebral cortex. Rather, they are arranged in a regional and laminar fashion that span a range of scales. Here we demonstrate an innovative imaging and analysis pipeline to construct a reliable cell census across the human cerebral cortex. Magnetic resonance imaging (MRI) is used to establish a macroscopic reference coordinate system of laminar and cytoarchitectural boundaries. Cell counting is obtained with both traditional immunohistochemistry, to provide a stereological gold-standard, and with a custom-made inverted confocal light-sheet fluorescence microscope (LSFM) for 3D imaging at cellular resolution. Finally, mesoscale optical coherence tomography (OCT) enables the registration of the distorted histological cell typing obtained with LSFM to the MRI-based atlas coordinate system.

Competing Interest Statement

BF has a financial interest in CorticoMetrics, a company whose medical pursuits focus on brain imaging and measurement technologies. BF's interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies.

Footnotes

  • ↵† These authors have supervised this work and share last authorship

  • https://dandiarchive.org/dandiset/000026/draft

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 21, 2021.
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A multimodal imaging and analysis pipeline for creating a cellular census of the human cerebral cortex
Irene Costantini, Leah Morgan, Jiarui Yang, Yael Balbastre, Divya Varadarajan, Luca Pesce, Marina Scardigli, Giacomo Mazzamuto, Vladislav Gavryusev, Filippo Maria Castelli, Matteo Roffilli, Ludovico Silvestri, Jessie Laffey, Sophia Raia, Merina Varghese, Bridget Wicinski, Shuaibin Chang, Anderson Chen I-Chun, Hui Wang, Devani Cordero, Matthew Vera, Jackson Nolan, Kim Nestor, Jocelyn Mora, Juan Eugenio Iglesias, Erendira Garcia Pallares, Kathryn Evancic, Jean Augustinack, Morgan Fogarty, Adrian V. Dalca, Matthew Frosch, Caroline Magnain, Robert Frost, Andre van der Kouwe, Shih-Chi Chen, David A. Boas, Francesco Saverio Pavone, Bruce Fischl, Patrick R. Hof
bioRxiv 2021.10.20.464979; doi: https://doi.org/10.1101/2021.10.20.464979
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A multimodal imaging and analysis pipeline for creating a cellular census of the human cerebral cortex
Irene Costantini, Leah Morgan, Jiarui Yang, Yael Balbastre, Divya Varadarajan, Luca Pesce, Marina Scardigli, Giacomo Mazzamuto, Vladislav Gavryusev, Filippo Maria Castelli, Matteo Roffilli, Ludovico Silvestri, Jessie Laffey, Sophia Raia, Merina Varghese, Bridget Wicinski, Shuaibin Chang, Anderson Chen I-Chun, Hui Wang, Devani Cordero, Matthew Vera, Jackson Nolan, Kim Nestor, Jocelyn Mora, Juan Eugenio Iglesias, Erendira Garcia Pallares, Kathryn Evancic, Jean Augustinack, Morgan Fogarty, Adrian V. Dalca, Matthew Frosch, Caroline Magnain, Robert Frost, Andre van der Kouwe, Shih-Chi Chen, David A. Boas, Francesco Saverio Pavone, Bruce Fischl, Patrick R. Hof
bioRxiv 2021.10.20.464979; doi: https://doi.org/10.1101/2021.10.20.464979

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