02966nas a2200397   4500000000100000000000100001008004100002260001500043100002300058700001900081700002100100700001600121700002300137700002000160700002000180700002000200700002000220700001900240700001600259700002000275700001800295700001700313700002400330700001900354700001800373700002000391700001900411700002200430700002100452700002100473700002100494700002600515245011700541856006400658520184600722       2024                            d  c2024-02-061 aAdrià Casamitjana1 aMatteo Mancini1 aEleanor Robinson1 aLoïc Peter1 aRoberto Annunziata1 aJuri Althonayan1 aShauna Crampsie1 aEmily Blackburn1 aBenjamin Billot1 aAlessia Atzeni1 aOula Puonti1 aYaël Balbastre1 aPeter Schmidt1 aJames Hughes1 aJean C. Augustinack1 aBrian L. Edlow1 aLilla Zöllei1 aDavid L. Thomas1 aDorit Kliemann1 aMartina Bocchetta1 aCatherine Strand1 aJanice L. Holton1 aZane Jaunmuktane1 aJuan Eugenio Iglesias00aA next-generation, histological atlas of the human brain and its application to automated brain MRI segmentation  uhttps://www.biorxiv.org/content/10.1101/2024.02.05.579016v13 aMagnetic resonance imaging (MRI) is the standard tool to image the human brain in vivo. In this domain, digital brain atlases are essential for subject-specific segmentation of anatomical regions of interest (ROIs) and spatial comparison of neuroanatomy from different subjects in a common coordinate frame. High-resolution, digital atlases derived from histology (e.g., Allen atlas [3], BigBrain [4], Julich [5]), are currently the state of the art and provide exquisite 3D cytoarchitectural maps, but lack probabilistic labels throughout the whole brain. Here we present NextBrain, a next-generation probabilistic atlas of human brain anatomy built from serial 3D histology and corresponding highly granular delineations of five whole brain hemispheres. We developed AI techniques to align and reconstruct ∼10,000 histological sections into coherent 3D volumes, as well as to semi-automatically trace the boundaries of 333 distinct anatomical ROIs on all these sections. Comprehensive delineation on multiple cases enabled us to build an atlas with probabilistic labels throughout the whole brain. Further, we created a companion Bayesian tool for automated segmentation of the 333 ROIs in any in vivo or ex vivo brain MRI scan using the NextBrain atlas. We showcase two applications of the atlas: automated segmentation of ultra-high-resolution ex vivo MRI and volumetric analysis of brain ageing based on ∼4,000 publicly available in vivo MRI scans. We publicly release the raw and aligned data (including an online visualisation tool), probabilistic atlas, and segmentation tool. By enabling researchers worldwide to analyse brain MRI scans at a superior level of granularity without manual effort or highly specific neuroanatomical knowledge, NextBrain will accelerate our quest to understand the human brain in health and disease.