A cellular resolution atlas of Broca’s area
Irene Costantini, Leah Morgan, Jiarui Yang, Yaël 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, Hui Wang, Devani Cordero, Matthew Vera, Jackson Nolan, Kimberly Nestor, Jocelyn Mora, Juan Eugenio Iglesias, Erendira Garcia Pallares, Kathryn Evancic, Jean C. Augustinack, Morgan Fogarty, Adrian V. Dalca, Matthew P. Frosch, Caroline Magnain, Robert Frost, André van der Kouwe, Shih‐Chi Chen, David A. Boas, Francesco S. Pavone, Bruce Fischl, Patrick R. Hof
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.