A cellular resolution atlas of Broca’s area

Year: 2023

Authors: Costantini I., Morgan L., Yang JR., Balbastre Y., Varadarajan D., Pesce L., Scardigli M., Mazzamuto G., Gavryusev V., Castelli FM., Roffilli M., Silvestri L., Laffey J., Raia S., Varghese M., Wicinski B., Chang SB., Chen IA., Wang H., Cordero D., Vera M., Nolan J., Nestor K., Mora J., Iglesias JE., Pallares EG., Evancic K., Augustinack JC., Fogarty M., Dalca AV., Frosch MP., Magnain C., Frost R., van der Kouwe A., Chen SC., Boas DA., Pavone FS., Fischl B., Hof PR.

Autors Affiliation: Univ Florence, European Lab Nonlinear Spect LENS, Sesto Fiorentino, FI, Italy; Univ Florence, Dept Biol, Florence, Italy; Natl Res Council CNR, Natl Inst Opt INO, Sesto Fiorentino, Italy; Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA; Boston Univ, Dept Biomed Engn, Boston, MA USA; Harvard Med Sch, Dept Radiol, Boston, MA USA; Univ Florence, Dept Phys & Astron, Sesto Fiorentino, FI, Italy; Univ Florence, Dept Expt & Clin Med, Div Physiol, Florence, Italy; Bioret srl, Cesena, Italy; Icahn Sch Med Mt Sinai, Nash Family Dept Neurosci, New York, NY USA; Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY USA; Boston Univ, Dept Elect & Comp Engn, Boston, MA USA; UCL, Dept Med Phys & Biomed Engn, London, England; MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA USA; Washington Univ McKelvey Sch Engn, Imaging Sci Program, Dept Biomed Engn, St. Louis, MO USA; Washington Univ, Dept Radiol, Sch Med, St. Louis, MO USA; Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA USA; Harvard Med Sch, Boston, MA USA; Univ Cape Town, Dept Human Biol, Cape Town, South Africa; Chinese Univ Hong Kong, Dept Mech & Automat Engn, Shatin, Hong Kong, Peoples R China; MIT, HST, 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.

Journal/Review: SCIENCE ADVANCES

Volume: 9 (41)      Pages from: eadg3844-1  to: eadg3844-14

More Information: Support for this research was provided in part by the BRAIN Initiative Cell Census Network grant U01 MH117023; The National Institute for Biomedical Imaging and Bioengineering P41 EB015896, R01 EB023281, R01 EB006758, R21E B018907, R01 EB019956, P41 EB030006, and R00 EB023993; The National Institute on Aging R56 AG064027, R01 AG064027, R01 AG008122, and R01 AG016495; The National Institute of Mental Health R01 MH123195, R01 MH121885, and RF1 MH123195; The National Institute for Neurological Disorders and Stroke R01 NS0525851, R21 NS072652, R01 NS070963, R01 NS083534, U01 NS086625, U24 NS10059103, R01 NS105820, and R01 NS128843; Eunice Kennedy Shriver National Institute of Child Health and Human Development R21 HD106038; Chan-Zuckerberg Initiative DAF, an advised fund of Silicon Valley Community Foundation grant number 2019-198101; Shared Instrumentation Grants S10 RR023401, S10 RR019307, and S10 RR023043; NIH Blueprint for Neuroscience Research U01 MH093765, part of the multi-institutional Human Connectome Project; European Union’s Horizon 2020 research and innovation Framework Programme under grant agreement no. 654148 (Laserlab-Europe); European Union’s Horizon 2020 Framework Programme for Research and Innovation under the specific grant agreement no. 785907 (Human Brain Project SGA2) and no. 945539 (Human Brain Project SGA3); Marie Sklodowska-Curie grant agreement no. 793849 (MesoBrainMicr); Italian Ministry for Education in the framework of Euro-Bioimaging Italian Node (ESFRI research infrastructure); European Research Council (starting grant 677697, project BUNGEE-TOOLS); Alzheimer’s Research UK (Interdisciplinary grant ARUK-IRG2019A-003); The National Institute of Health R01 AG070988-01 and RF1 MH123195-01; and Fondazione CR Firenze (private foundation) Human Brain Optical Mapping. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health and other funding agencies.
KeyWords: Optical Coherence Tomography; Light-sheet Microscopy; Ultrahigh-resolution; Stereologic Analysis; Alzheimers-disease; Brain; Vulnerability; Neurons; Cells; Whole
DOI: 10.1126/sciadv.adg3844

ImpactFactor: 11.700
Citations: 7
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