A next-generation, histological atlas of the human brain and its application to automated brain MRI segmentation

Abstract

Magnetic resonance imaging (MRI) is the standard tool to image the human brain <i>in vivo.</i> 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 [7], BigBrain [13], Julich [15]), are currently the state of the art and provide exquisite 3D cytoarchitectural maps, but lack probabilistic labels throughout the whole brain. Here we present <i>NextBrain,</i> 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 with joint geometric constraints (no overlap or gaps between sections), 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 <i>the first probabilistic histological atlas of the whole human brain.</i> Further, we created a companion Bayesian tool for automated segmentation of the 333 ROIs in any <i>in vivo</i> or <i>ex vivo</i> brain MRI scan using the <i>NextBrain</i> atlas. We showcase two applications of the atlas: automated segmentation of ultra-high-resolution <i>ex vivo</i> MRI and volumetric analysis of Alzheimer's disease and healthy brain ageing based on ~4,000 publicly available <i>in vivo</i> MRI scans. We publicly release: the raw and aligned data (including an online visualisation tool); the probabilistic atlas; the segmentation tool; and ground truth delineations for a 100 μm isotropic <i>ex vivo</i> hemisphere (that we use for quantitative evaluation of our segmentation method in this paper). By enabling researchers worldwide to analyse brain MRI scans at a superior level of granularity without manual effort or highly specific neuroanatomical knowledge, <i>NextBrain</i> holds promise to increase the specificity of MRI findings and ultimately accelerate our quest to understand the human brain in health and disease.