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

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 A. Wicinski; Shuaibin Chang; Anderson Chen; Hui Wang; Devani Cordero; Matthew Vera; Jackson C. Nolan; Kimberly Nestor; Jocelyn Mora; Juan Eugenio Iglesias; Erendira Garcia Pallares; Kathryn Evancic; Jean C. Augustinack; Morgan Fogarty; Adrian Vasile Dalca

doi:10.1101/2021.10.20.464979

NeurosciencebioRxivOct 20, 2021

Preprint

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

Irene Costantini iD, Leah Morgan iD, Jiarui Yang iD, Yaël Balbastre iD, Divya Varadarajan iD, Luca Pesce iD, Marina Scardigli iD, Giacomo Mazzamuto iD, Vladislav Gavryusev iD, Filippo Maria Castelli iD, Matteo Roffilli iD, Ludovico Silvestri iD, Jessie Laffey iD, Sophia Raia iD, Merina Varghese iD, Bridget A. Wicinski iD, Shuaibin Chang iD, Anderson Chen iD, Hui Wang iD, Devani Cordero iD, Matthew Vera iD, Jackson C. Nolan iD, Kimberly Nestor iD, Jocelyn Mora iD, Juan Eugenio Iglesias iD, , Patrick R. Hof iD

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.

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